[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"apathy\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:apathy":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,19,0,[8,45,76,99,130,157,188,216,241,274,299,330,349,372,400,428,452,475,498],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":14,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":28,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100362412","phase-3-in-vivo-involvement-of-the-cholinergic-and-dopaminergic-systems-in-the-pathophysiology-of-apathy-100362412",false,"NCT03998852","In Vivo Involvement of the Cholinergic and Dopaminergic Systems in the Pathophysiology of Apathy.","ADACHOL","Inclusion Criteria:\n\n* Patient of legal age and younger than 75 years\n* Patient with a Rankin score less then or equal to 2 and with or without apathy, demonstrated by AI scales at 3 months after stroke (apathetic patient = AI scale score \\> 2)\n* Affiliate or beneficiary of a social security scheme\n* Subjects (female study subjects and female partners of male participants) using highly effective contraceptive methods (intra-uterine device, progestin or estrogen-progestin contraceptive, sterilization)\n* Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research)\n\nExclusion Criteria:\n\n* Patients over 75 years old\n* Taking of any pharmacological treatment likely to affect cholinergic systems at the time of PET-scan: Amitriptyline, Atropine, Brompheniramine, Chlorphenamine, Chlorpromazine, Clomipramine, Clozapine, Dimenhydrinate, Diphenhydramine, Doxepine, Hyoscyamine, Imipramine, Meclozine, Nortriptyline, Oxybutynine, Promethazine, Scopolamine, Trimipramine, Hydroxyzine.\n* Taking of any pharmacological treatment likely to affect dopaminergic systems at the time of PET-scan: glucagon, haloperidol, reserpin\n* Taking of any selective serotonine reuptake inhibitors treatment\n* White matter T2 hyperintense lesions (Fazekas score \\> 3)\n* NYHA Class III to IV Heart Failure Patient\n* Patients with allergy or conter-indication to entacapone\n* Subjects with positive pregnancy test (BHCG dosage and Urine dipstick), and\u002For currently breast-feeding\n* Patients unable to come back to hospital for at least 2-follow-up visits\n* Patient with a chronic neurological disorder or severe psychiatric disorder\n* Patient with cognitive impairment (MoCA\\\u003C24) and depression (CES-D score \\> 17 for men and \\>23 for women)\n* Patient presenting a counter-indication for MRI\n* Patient presenting a counter-indication for TEP with \\[18F\\]-FEOBV or \\[18F\\]-FDOPA (known allergy)\n* Patient who underwent a PET examination in the previous month\n* Patient with state of health not allowing a displacement in the department of imaging of the CHU: bedridden state, state of health very deteriorated\n* Patient deprived of liberty by judicial or administrative decision\n* Patient under legal protection or unable to express its own consent\n* Subject within exclusion period from another clinical trial","ALL","18 Years","75 Years",{"count":20,"type":21},30,"ESTIMATED","INTERVENTIONAL",[24],"PHASE3","Apathy is a neurocognitive syndrome characterized by reduced goal-directed behaviors, contributing to decreased patient and caregiver quality of life. Apathy pathophysiology involves disruption of cortico-striato-thalamo-cortical loops, modulated by several neurotransmitter systems including dopamine and acetylcholine, thus complexifying pharmacological management. Post-stroke apathy (PSA) can provide a proper in vivo model to study the underlying neurochemical substrates of apathy as a syndrome. The present project aims to provide a better characterization of the cholinergic and dopaminergic functioning in apathy as a syndrome.\n\nIn order to precise the respective alterations of these two systems, investigators will use a positron emission tomography (PET) molecular imaging of dopaminergic (with \\[18F\\]-FDOPA, a marker of the decarboxylating enzyme of dopamine) and - for the first time in apathetic patients - cholinergic (with \\[18F\\]-FEOBV, a marker of the vesicular acetylcholine transporter) transmissions in 15 apathetic and 15 unapathetic patients 3 months after stroke, without overlapping depression. This dual imaging study may provide help in guiding therapeutic management of PSA. The functional network analysis allowed by functional MRI is crucial to complement regional neurotransmitter deficits observed with PET. Altogether, a multimodal approach in apathy, combining PET and MRI, can allow identifying which circuits of the cortico-striato-thalamo-cortical loops are disrupted and how these circuits are modulated by other neurotransmitters.",[27],"Apathy",[27,29,30,31],"Stroke","Cholinergic neurotransmission","Dopaminergic neurotransmission","RECRUITING","2026-06-09",{"date":35,"type":36},"2026-06-10","ACTUAL",{"date":38,"type":36},"2021-04-13",{"date":40,"type":21},"2027-05-13",{"name":42,"class":43},"University Hospital, Bordeaux","OTHER",1,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":51,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":16,"minAge":53,"maxAge":4,"enrollmentInfo":54,"targetDuration":4,"studyType":22,"phases":56,"briefSummary":58,"conditions":59,"keywords":61,"overallStatus":65,"whyStopped":4,"lastUpdateSubmitDate":66,"lastUpdatePostDateStruct":67,"startDateStruct":69,"completionDateStruct":71,"leadSponsor":73,"locationsCount":75},"100628950","sensrem---sensoriality-and-multi-sensory-emotional-reminiscences-a-pilot-study-100628950","NCT07468305","SENS'REM - SENSoriality and Multi-Sensory Emotional Reminiscences: a Pilot Study","SENS'REM - SENSoriality and Multi-Sensory Emotional Reminiscences: Feasibility of Multi-Sensory Reminiscence in Virtual Reality on Apathy in Elderly People With Cognitive Disorders in Nursing Homes and Long-Term Care Units","SENS'REM","Inclusion Criteria:\n\n* Men or women aged 70 years or older\n* Living in a nursing home (EHPAD) or long-term care unit (USLD) for at least 3 months\n* Sufficient French language ability to understand the study procedures\n* Presence of apathy confirmed by a positive score on the Apathy Inventory\n* Moderate cognitive impairment documented by a Montreal Cognitive Assessment (MoCA) score between 10 and 17\n* Affiliated with a social security or health insurance system\n* Medical approval for virtual reality exposure (no contraindication)\n* Ability to provide informed consent, or consent provided by a legal representative or trusted person when applicable\n\nExclusion Criteria:\n\n* \"Diagnosed psychiatric disorder according to DSM-5 criteria (e.g., schizophrenia, bipolar disorder)\n* Severe or acute behavioral disturbances incompatible with study participation\n* Neurological comorbidities incompatible with virtual reality use (e.g., Lewy body disease, history of epilepsy)\n* Severe sensory impairment (vision, hearing, or olfaction) preventing participation\n* Known susceptibility to cybersickness based on the CyberSickness in Virtual Reality Questionnaire (CSQ-VR)\n* Presence of a cardiac pacemaker incompatible with virtual reality headset use\n* Withdrawal of informed consent at any time during the study\"","65 Years",{"count":55,"type":21},10,[57],"NA","SENS'REM is a pilot feasibility study evaluating a new non-drug therapeutic program based on multisensory reminiscence using immersive virtual reality in older adults living in nursing homes or long-term care units who present cognitive impairment and apathy.\n\nApathy is a frequent symptom in people with neurocognitive disorders. It is characterized by a loss of motivation, reduced interest in activities, and decreased emotional engagement. Apathy strongly affects quality of life, social interactions, and participation in care, and current drug treatments have limited effectiveness. For this reason, non-pharmacological approaches are increasingly recommended.\n\nThe SENS'REM program combines virtual reality with personalized multisensory stimulation (visual, auditory, olfactory and gustatory) to help participants relive meaningful autobiographical memories in an immersive and emotionally engaging environment. Each participant receives one session per week for six weeks. The content of the sessions is adapted to the individual life history of each participant.\n\nThe primary objective of this study is to evaluate the feasibility of implementing this program in institutional settings, including recruitment, organization, technical aspects, and participant adherence. Secondary objectives include evaluating changes in apathy, quality of life, cognitive functioning, social engagement, participant satisfaction, and the tolerance of the intervention.\n\nThe main hypothesis of the study is that a personalized multisensory virtual reality reminiscence program is feasible in nursing home and long-term care settings and may contribute to a reduction in apathy and an improvement in engagement and well-being among older adults with cognitive impairment.\n\nThis pilot study will provide essential preliminary data to optimize the intervention and prepare a future larger comparative clinical trial.",[27,60],"Apathy in Dementia",[62,63,64],"Neurocognitive disorders","apathy","dementia","NOT_YET_RECRUITING","2026-05-21",{"date":68,"type":36},"2026-05-26",{"date":70,"type":21},"2026-09",{"date":72,"type":21},"2027-08",{"name":74,"class":43},"Centre Hospitalier Universitaire de Nice",2,{"id":77,"slug":78,"hasResults":11,"nctId":79,"briefTitle":80,"officialTitle":80,"acronym":81,"eligibilityCriteria":82,"healthyVolunteers":11,"sex":16,"minAge":83,"maxAge":4,"enrollmentInfo":84,"targetDuration":4,"studyType":22,"phases":86,"briefSummary":87,"conditions":88,"keywords":89,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":91,"lastUpdatePostDateStruct":92,"startDateStruct":94,"completionDateStruct":95,"leadSponsor":97,"locationsCount":75},"100624036","robotic-technologies-for-apathy-in-dementia-a-randomised-controlled-trial-raphael-100624036","NCT07404410","Robotic Technologies for APATHy in Dementia: a Randomised Controlled Trial (RAPHAel)","RAPHAel","Inclusion Criteria:\n\n* Age 40 years or older\n* Clinical diagnosis of a neurocognitive disorder, including: Mild cognitive impairment (MCI) or mild behavioral impairment (MBI), or Major neurocognitive disorder (dementia), due to Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, or other neurodegenerative diseases.\n* Presence of clinically relevant apathy, defined as a score greater than 2 on the apathy domain (G) of the Neuropsychiatric Inventory (NPI).\n* Preserved ability to understand and produce spoken and written language sufficient to participate in the intervention and assessments.\n* Absence of clinically significant agitation or aggressiveness, defined as a score lower than 2 on the agitation\u002Faggression domain (C) of the NPI.\n* Adequate educational and occupational history sufficient to exclude intellectual disability.\n* Availability of a study partner (family member, friend, or caregiver) who: Knows the participant well, Has contact with the participant for at least 10 hours per week, Is able to complete questionnaires about the participant, Is able to read, understand, and speak Italian, and Provides independent informed consent for participation.\n* Ability and willingness of the participant (and study partner, when applicable) to provide informed consent.\n\nExclusion criteria:\n\n* Refusal or withdrawal of informed consent by the participant or the study partner.\n* History or current evidence of neurological conditions other than the target neurodegenerative diseases that may affect cognitive function (e.g., major stroke, brain tumor, normal pressure hydrocephalus, traumatic brain injury).\n* History or current diagnosis of major psychiatric disorders that could interfere with study participation or assessments.\n* Presence of medical conditions that may significantly affect cognitive function (e.g., severe renal or hepatic failure, untreated obstructive sleep apnea, hypothyroidism, vitamin B12 deficiency).\n* Clinically significant agitation or aggressiveness, defined as a score of 2 or higher on the agitation\u002Faggression domain (C) of the Neuropsychiatric Inventory (NPI).\n* Inability to understand or communicate in Italian sufficient to complete study procedures.\n* Absence of an eligible study partner or withdrawal of consent by the study partner.","40 Years",{"count":85,"type":21},75,[57],"The goal of this trial is to learn whether home-based robotic interventions can reduce apathy in people with cognitive decline. Apathy means reduced motivation, interest, or initiative in daily life. It is a common and distressing symptom in people with mild cognitive impairment (MCI) or dementia and can strongly affect both participants and their caregivers.\n\nThis study will compare two different robotic interventions with standard occupational therapy. Researchers want to understand if these new technologies can help people become more engaged, motivated, and involved in everyday activities, and whether they also reduce stress and improve quality of life for caregivers.\n\nThe main questions this study aims to answer are:\n\n* Do robotic interventions reduce apathy more than standard occupational therapy?\n* Are these robotic interventions easy to use and acceptable for people with cognitive impairment?\n* Do these interventions reduce caregiver stress and improve caregiver quality of life?\n\nParticipants will be adults over 40 years of age with a diagnosis of mild cognitive impairment or dementia caused by a neurodegenerative disease, such as Alzheimer's disease, frontotemporal dementia, or dementia with Lewy bodies. All participants must show clinically relevant apathy and have a family member or caregiver who can support them during the study and answer questionnaires.\n\nParticipants will be randomly assigned to one of three groups:\n\n* A telepresence robot group, where participants interact at home with a therapist through a remotely controlled robot that delivers personalized cognitive stimulation.\n* A social robot group, where participants interact at home with a humanoid robot that holds personalized conversations on topics of interest.\n* A control group receiving home-based occupational therapy, which is the current standard care for behavioral symptoms.\n\nEach intervention lasts six weeks and takes place in the participant's home. The robotic interventions are designed to fit into daily routines and can be adapted to the participant's abilities and preferences. Occupational therapy sessions focus on meaningful activities, environmental adaptations, and caregiver support.\n\nParticipants will complete assessments at three time points: before the intervention, at the end of the six-week intervention, and eight weeks after the intervention ends. These assessments include interviews, questionnaires, and simple tasks to measure apathy, emotional responses, social interaction, and quality of life. Caregivers will also complete questionnaires about stress and daily burden.\n\nResearchers will also collect information about how often and how participants interact with the robots, such as how long conversations last and how engaged participants appear. These data will help researchers understand how robotic interactions relate to changes in apathy and behavior.\n\nThis study aims to provide evidence on whether robotic technologies can be safely and effectively used at home to support people with cognitive impairment and apathy. The results may help develop new non-drug treatments and improve care options for people living with dementia and their caregivers.",[27,60],[64,63,90],"robotics","2026-04-28",{"date":93,"type":36},"2026-05-05",{"date":91,"type":36},{"date":96,"type":21},"2026-11-30",{"name":98,"class":43},"Giovanna Zamboni",{"id":100,"slug":101,"hasResults":11,"nctId":102,"briefTitle":103,"officialTitle":104,"acronym":105,"eligibilityCriteria":106,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":107,"enrollmentInfo":108,"targetDuration":4,"studyType":110,"phases":4,"briefSummary":111,"conditions":112,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":120,"lastUpdatePostDateStruct":121,"startDateStruct":123,"completionDateStruct":125,"leadSponsor":127,"locationsCount":129},"100604206","esketamine-nasal-spray-in-real-world-settings-in-treatment-resistant-depression-100604206","NCT07146503","Esketamine Nasal Spray in Real-World Settings in Treatment-Resistant Depression","ESKPSY: Esketamine in Real-World Settings: Clinical Outcomes, Predictors of Response, Life Functioning and Biological Pathways","ESKPSY","Inclusion criteria were: (a) age 18-74, (b) DSM-5 diagnosis of a major depressive episode (MDE), (c) failure to respond to at least 2 prior antidepressant treatments (ADTs), and (d) current treatment with an SSRI or SNRI for which esketamine nasal spray was deemed appropriate.","74 Years",{"count":109,"type":21},100,"OBSERVATIONAL","This observational study investigates the use of Esketamine Intranasal Spray in patients with Treatment-Resistant Depression in Real-World Settings. The study aims to evaluate the clinical outcomes, including efficacy and safety, of esketamine treatment. It also explores predictors of treatment response, focusing on biological pathways such as genetics, neuroimaging, and psychophysical measures. Additionally, the study examines how esketamine impacts patients' life functioning, including social and occupational aspects. The goal is to better understand who benefits most from esketamine and how it affects daily life, to improve personalized care for patients with difficult-to-treat depression.",[113,114,115,27,116,117,118,119],"Depression and Quality of Life","Treatment Resistant Depression (TRD)","Anhedonia","Anxiety","Cognition","Temperament","Psychiatric Comorbidities","2026-03-25",{"date":122,"type":36},"2026-03-31",{"date":124,"type":36},"2022-11-01",{"date":126,"type":21},"2030-08",{"name":128,"class":43},"Riccardo Guglielmo",5,{"id":131,"slug":132,"hasResults":11,"nctId":133,"briefTitle":134,"officialTitle":135,"acronym":4,"eligibilityCriteria":136,"healthyVolunteers":11,"sex":16,"minAge":83,"maxAge":137,"enrollmentInfo":138,"targetDuration":4,"studyType":22,"phases":140,"briefSummary":141,"conditions":142,"keywords":144,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":148,"lastUpdatePostDateStruct":149,"startDateStruct":151,"completionDateStruct":153,"leadSponsor":155,"locationsCount":44},"100478057","targeting-apathy-with-music-in-parkinsons-disease-100478057","NCT05505019","Targeting Apathy With Music in Parkinson's Disease","The Role of a Personalized Music Intervention Towards Alleviating Apathy in Parkinson's Disease","Inclusion Criteria:\n\n\\- Clinical diagnosis of Parkinson's Disease following MDS Parkinson's disease criteria\n\nExclusion Criteria:\n\n* Participants with atypical Parkinsonism (eg. Progressive supranuclear palsy, multiple system atrophy, drug induced, etc.)\n* Epilepsy\n* Other neurological disease\u002Fcomplications (eg. myopathy, stroke, brain lesion, MS)\n* Significant cognitive impairment (MoCa \\\u003C21)\n* Moderate depression (Beck's Depression Inventory \\>20)\n* Severe\u002Fmultiple head trauma(s)\n* Participants with metal\u002Fmedical implants, including any of the following: artificial heart valve, brain aneurysm clip, electrical stimulators, ear or eye implant, implanted drug infusion pump, coil, catheter, or filter in any blood vessel, orthopedic hardware such as artificial joint, plate, and\u002For screws, other metallic prostheses, shrapnel, bullets, or other metal fragments, surgery or tattoos, including tattooed eyeliner, in the last six weeks, cardiac pacemaker, wires or defibrillator, or ferromagnetic aneurysm clip)\n* Participants who have gone through specific injuries\u002Fbrain surgery (eg. an injury where a piece of metal lodged in the eye or orbit)","85 Years",{"count":139,"type":21},50,[57],"Parkinson's Disease (PD) is often accompanied by non-motor symptoms that make treatment more difficult. One such symptom is apathy (lack of motivation and emotion). There are no treatments for apathy in PD, and this remains a major unmet need in PD patients. One possible way to target apathy in PD patients is listening to music, which has been shown to help improve apathy in older adults. Little work has explored the mechanism in which music targets apathy. Thus, the goal of this study is to understand how music listening can impact the brain towards decreasing apathy in PD patients.",[143,27],"Parkinson Disease",[145,146,147],"Music","Music intervention","Non-motor symptoms","2026-03-19",{"date":150,"type":36},"2026-03-23",{"date":152,"type":36},"2022-02-09",{"date":154,"type":21},"2026-07-31",{"name":156,"class":43},"University of British Columbia",{"id":158,"slug":159,"hasResults":11,"nctId":160,"briefTitle":161,"officialTitle":162,"acronym":4,"eligibilityCriteria":163,"healthyVolunteers":11,"sex":16,"minAge":164,"maxAge":4,"enrollmentInfo":165,"targetDuration":4,"studyType":110,"phases":4,"briefSummary":167,"conditions":168,"keywords":172,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":178,"lastUpdatePostDateStruct":179,"startDateStruct":181,"completionDateStruct":183,"leadSponsor":185,"locationsCount":129},"100611163","effects-of-personalized-digital-reminiscence-therapy-on-patients-with-neurocognitive-disorders-100611163","NCT07237009","Effects of Personalized Digital Reminiscence Therapy on Patients With Neurocognitive Disorders","Effects of Personalized Reminiscence Sessions Delivered by a Digital Conversational Agent to Patients With Neurocognitive Disorders","Inclusion Criteria:\n\n* Men and women over 60 years of age.\n* DSM-5 diagnosis: Early stage of major neurocognitive disorders or MCI (Mild Cognitive Impairment) including all underlying causes.\n* Have a Mini-Mental State Exam score of 21 ≤ MMSE ≤ 28.\n* Presence of mild or moderate depression, or presence of mild or moderate apathy, or presence of both\n* Displays the necessary physical and cognitive abilities, without major limitations compromising interaction with the digital tool.\n* Having voluntarily and informedly agreed to participate in the study (signed written consent).\n* Subject's ability to hear and see the digital tool's stimuli (tests integrated into the tool).\n* Patients with access to an Apple device (smartphone or tablet), either personal or provided by the sponsor, running iOS version 16 or higher, with internet access.\n* Patient has at least one close referent who declares their wish to contribute to the collection of biographical information via the digital messaging group.\n* Subjects covered by a social security scheme.\n\nExclusion Criteria:\n\n* Patients with moderate or severe dementia (MMSE score ≤ 20) because implicit memory recall is less effective in moderate or severe stages for people with PWD.\n* Presence of major psychiatric disorders (e.g., schizophrenia, severe major depressive episode, bipolar disorder).\n* Major hearing or visual impairments.\n* History of premorbid intellectual disability.\n* Patients under guardianship, conservatorship, or legal protection.\n* Patients who have already used the Lilia app\n* Participating simultaneously in another study involving human subjects, a clinical investigation, or a therapeutic trial for the entire duration of the study.\n* Patients who have received a new treatment related to neurocognitive disorders (medication) during the 3 months prior to the inclusion visit.","60 Years",{"count":166,"type":21},80,"This study aims to observe the effects of daily personalized digital reminiscence sessions, conducted with the help of a digital conversational agent, and to determine whether these sessions lead to improvements in symptoms such as apathy and depression.\n\nThe researchers therefore seek to observe whether this daily use can improve certain aspects of well-being, such as motivation, mood, sleep quality, quality of life, and engagement with the tool.\n\nThe study also aims to assess whether simple reminders delivered via the application are sufficient to encourage regular use without external assistance.\n\nParticipants will:\n\n* Use the reminiscence app for 25 days for 10-15 minutes.\n* Have a primary caregiver help personalize the app by sharing family memories, other relatives may optionally contribute in a private group.\n* Complete brief questionnaires at the start and during follow-up routine visits (for example, apathy and depression scales, sleep, and quality of life).",[169,170,171,27,60],"Neurocognitive Disorders, Mild","Cognitive Impairment, Mild","Depression Mild",[173,174,27,175,176,177],"Mild Cognitive Impairment","Dementia","Mild Depression","Digital Reminiscence therapy","personalized Reminiscence therapy","2026-03-06",{"date":180,"type":36},"2026-03-09",{"date":182,"type":36},"2025-10-14",{"date":184,"type":21},"2026-12",{"name":186,"class":187},"KompanionCare SAS","INDUSTRY",{"id":189,"slug":190,"hasResults":11,"nctId":191,"briefTitle":192,"officialTitle":193,"acronym":194,"eligibilityCriteria":195,"healthyVolunteers":11,"sex":16,"minAge":196,"maxAge":197,"enrollmentInfo":198,"targetDuration":4,"studyType":22,"phases":199,"briefSummary":202,"conditions":203,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":206,"lastUpdatePostDateStruct":207,"startDateStruct":209,"completionDateStruct":211,"leadSponsor":213,"locationsCount":215},"100628406","phase-1-safety-and-tolerability-of-irl757-in-participants-with-parkinsons-disease-and-apathy-100628406","NCT07461220","Safety and Tolerability of IRL757 in Participants With Parkinson's Disease and Apathy","A Phase 1b, Prospective, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Safety and Tolerability of Multiple Oral Doses of IRL757 in Participants With Parkinson's Disease and Apathy","LIFT-PD","Inclusion Criteria:\n\n1. Male and female participants between 50 and 90 years of age, inclusive, with diagnosed Parkinson's disease according to the Movement Disorders Society Clinical Diagnostic Criteria for Parkinson's disease.\n2. Hoehn and Yahr stage ≤ 4 at screening.\n3. MoCA score of 20 or greater at screening and baseline.\n4. Meets the ISCTM definition of apathy (criterion B), defined as exhibiting ≥ 1 symptom in ≥ 2 of the following 3 dimensions, that is persistent or frequently recurrent (ie, ≥ 3 days per week) for ≥ 4 weeks prior to screening:\n\n   * Diminished initiative (less spontaneous and\u002For active than usual self; less likely to initiate usual activities such as hobbies, chores, self-care, conversation, work-related or social activities),\n   * Diminished interest (less enthusiastic about usual activities, less interested in, or less curious about, events in their environment, less interested in activities and plans made by others, less interested in friends and family, less persistence in maintaining or completing tasks or activities), or\n   * Diminished emotional expression\u002Fresponsiveness (less spontaneous emotions, less affectionate compared to their usual self, expresses less emotion in response to positive or negative events, less concerned about the impact of their actions on other people, less empathy).\n\n   The symptoms must represent a significant change from the participant's usual behaviour and cause significant impairment in personal, social, or occupational functioning. Finally, the symptoms must not be due to psychiatric illness, intellectual disability, physical\u002Fmotor disabilities, or changes in level of consciousness or the effects of substances.\n5. Participants with moderate to severe apathy based on a score of at least -16 on the LARS at screening and baseline.\n6. Availability of the primary caregiver, any adult who spends greater than 10 hours a week with the participant and supervises his or her care, to accompany the participant to trial visits and to participate in the trial.\n7. Treatment with anti-Parkinson drugs, antidepressants (except for those listed as prohibited medications in the protocol), and Choline esterase inhibitors is permitted if doses are stable for 1 month before randomization and remain stable during the trial.\n\nExclusion Criteria:\n\nParticipants will be excluded if they meet any of the following exclusion criteria when assessed:\n\n1. Any active, current psychiatric comorbidity (such as major depressive disorder, obsessive-compulsive disorder, etc)\n\n   1. as assessed by the MINI at screening,\n   2. as assessed by the MADRS at the baseline visit with a score \\> 18.\n2. Score of \\> 2 in the MDS-UPDRS Part 1, Question 1.2 (hallucinations and psychosis).\n3. Need for acute psychiatric hospitalization.\n4. Participants who:\n\n   1. Answer \"Yes\" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) within the last 6 months prior to screening or the baseline visit, OR\n   2. Answer \"Yes\" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) within the last 6 months prior to screening or at the baseline visit, OR\n   3. Answer \"Yes\" on any of the 5 C-SSRS Suicidal Behaviour Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behaviour) within 2 years prior to screening or at the baseline visit, OR\n   4. In the opinion of the investigator, present a serious risk of suicide.\n5. Subthalamic stimulation of less than 1 year from screening.\n6. Subthalamic stimulation without stable parameters for 3 months from screening.\n7. Clinically significant impulse control disorders (ICDs) as assessed by the QUIP RS (score \\> 6).\n8. Renal impairment (estimated glomerular filtration rate \\[eGFR\\] \\\u003C 30 mL\u002Fmin\u002F1.73m2 calculated based on cystatin C).\n9. Moderately impaired hepatic function or advanced hepatic dysfunction as assessed by a Child Pugh score B or C.\n10. Significant communicative impairments that prohibit meaningful participation in the trial assessments.\n11. Central nervous system abnormalities (eg, cerebral aneurysm) and\u002For other vascular abnormalities such as vasculitis or pre-existing stroke, motor tics, or family history or diagnosis of Tourette's syndrome, seizures (convulsions, epilepsy), or historical clinically significant abnormal electroencephalograms (EEGs).\n12. History of cancer within 5 years prior to screening, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non metastatic prostate cancer, or in situ cervical cancer. The cancer must not be active or currently under treatment except for potentially long-term stable medications.\n13. Any clinically significant illness, medical\u002Fsurgical procedure, or trauma within 4 weeks of the first administration of IMP.\n14. Any planned major surgery within the duration of the trial.\n15. Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody, or HIV.\n16. Any vital signs values outside of the following ranges after 10 minutes of supine rest at the time of screening:\n\n    1. Systolic blood pressure (SBP) \\> 150 mmHg\n    2. Diastolic blood pressure (DBP) \\> 90 mmHg\n    3. Heart rate \\\u003C 50 or \\> 100 beats per minute.\n17. Participants with a history of hypertension must have stable blood pressure for the 3 months prior to the trial, defined as blood pressure \\\u003C 150\u002F90 mmHg. If this criterion is not met the participant is not eligible for the trial.\n18. Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF) \\> 450 msec for male participants or \\> 470 msec for female participants, cardiac arrhythmias, or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the investigator.\n19. History of severe allergy\u002Fhypersensitivity or ongoing allergy\u002Fhypersensitivity, as judged by the investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to IRL757.\n20. Current nicotine use; irregular nicotine use less than 3 times per week is allowed before the screening visit.\n21. Positive screen for illicit drugs (including cannabinoids) and\u002For abuse or positive screen for alcohol at screening or on Day 1 prior to administration of the IMP.\n22. Use of anabolic steroids.\n23. Use of antipsychotics.\n24. The participant is unwilling or unable to discontinue taking alpha-2 adrenergic receptor antagonists and\u002For cytochrome P450 (CYP) inhibitor or substrate drugs at least 14 days or 5 times the half-life of the drug (whichever is longer) before randomization.\n25. Excessive or variable daily caffeine consumption (ie, exceeding 3 cups per day) for the 2 weeks prior to screening.\n26. Plasma donation within 1 month of screening or any blood donation\u002Fblood loss \\> 450 mL during the 3 months prior to screening.\n27. Participants who are breastfeeding.\n28. Participants who have a positive pregnancy test result prior to receiving IMP.\n29. Heterosexually active participants of reproductive potential (PORP) \u002F POCBP who do not agree to use a highly effective method of birth control or remain fully abstinent from sexual activity with the potential for conception. Female participants of nonchildbearing potential (permanently sterilized \\[ie, hysterectomy, bilateral oophorectomy\\], postmenopausal for at least 12 months, or otherwise incapable of pregnancy) and male participants who have had a bilateral orchiectomy are eligible for enrolment.\n30. Participants who do not agree to refrain from donating sperm or eggs from trial screening through 90 days (for sperm) and 30 days (for eggs) after the last dose of IMP.\n31. Participants who have participated in a clinical trial involving an investigational drug or device within the last 90 days or who participated in more than 2 clinical trials involving an investigational drug or device within the past year.\n32. The investigator considers the participant unlikely to comply with trial procedures, restrictions, and requirements.\n33. Any condition that, in the opinion of the investigator, makes it medically inappropriate or risky for the participant to enrol in the trial.","50 Years","90 Years",{"count":85,"type":21},[200,201],"PHASE1","PHASE2","This clinical trial's goal is to evaluate if the IRL757 is safe and has a good tolerability in participants with Parkinson's disease and experiencing apathy (a lack of interest or motivation). In addition, the trial is aiming to learn if IRL757 has effects on the symptoms of Parkinson's disease. Researchers will compare the effects of IRL757 to a placebo (a look-alike substance that contains no drug).\n\nParticipants who fit the study criteria will be treated with the study drug (either the active drug IRL757 or placebo) for 12 weeks and will visit the clinic at 5 defined timepoints for check-ups and tests. A follow-up call after the end of treatment will be done 4 weeks after the last study drug intake.",[204,27,205],"PARKINSON DISEASE (Disorder)","Safety","2026-03-04",{"date":208,"type":36},"2026-03-10",{"date":210,"type":36},"2026-02-18",{"date":212,"type":21},"2027-05",{"name":214,"class":187},"Integrative Research Laboratories AB",13,{"id":217,"slug":218,"hasResults":11,"nctId":219,"briefTitle":220,"officialTitle":221,"acronym":222,"eligibilityCriteria":223,"healthyVolunteers":11,"sex":16,"minAge":164,"maxAge":4,"enrollmentInfo":224,"targetDuration":4,"studyType":22,"phases":225,"briefSummary":226,"conditions":227,"keywords":230,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":232,"lastUpdatePostDateStruct":233,"startDateStruct":235,"completionDateStruct":237,"leadSponsor":239,"locationsCount":44},"100586724","a-virtual-life-story-club-intervention-to-improve-loneliness-and-apathy-in-community-dwelling-older-adults-100586724","NCT06919094","A Virtual Life Story Club Intervention to Improve Loneliness and Apathy in Community-Dwelling Older Adults","A Virtual Life Story Club Intervention to Improve Loneliness and Apathy in Community-Dwelling Older Adults: A Mixed-Methods Feasibility Study","LSC Feasible","Inclusion Criteria:\n\n* Age 60 and over\n* English or Spanish fluency\n* Able to provide informed consent\n\nExclusion Criteria:\n\n* Dementia based on Aging and Dementia (AD8) score of ≥4 or previous dementia diagnosis\n* Severe auditory or visual loss\n* Lack of access to internet connection or phone",{"count":139,"type":21},[57],"Reminiscence therapy is a non-invasive, non-pharmacological intervention that has been shown to improve cognition, mood, functional status, quality of life, and apathy in older adults. Group reminiscence therapy combines structured social engagement and recounting of personal stories that address both social connection (a risk factor for cognitive decline) and cognition. Life story club© (LSC) is an established, non-profit organization that provides virtual, group reminiscence therapy for older adults to reduce loneliness and promote a sense of belonging and has not been formally studied.",[27,228,229],"Loneliness","Reminiscence Therapy",[27,231,228,229],"Social Isolation","2025-12-17",{"date":234,"type":36},"2025-12-19",{"date":236,"type":36},"2025-08-15",{"date":238,"type":21},"2026-08-31",{"name":240,"class":43},"Montefiore Medical Center",{"id":242,"slug":243,"hasResults":11,"nctId":244,"briefTitle":245,"officialTitle":246,"acronym":247,"eligibilityCriteria":248,"healthyVolunteers":11,"sex":16,"minAge":4,"maxAge":4,"enrollmentInfo":249,"targetDuration":4,"studyType":22,"phases":251,"briefSummary":252,"conditions":253,"keywords":258,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":265,"lastUpdatePostDateStruct":266,"startDateStruct":268,"completionDateStruct":270,"leadSponsor":272,"locationsCount":44},"100614449","phase-2-combined-brain-stimulation-and-methylphenidate-treatment-for-apathy-in-dementia-100614449","NCT07279740","Combined Brain Stimulation and Methylphenidate Treatment for Apathy in Dementia","Methylphenidate Primed iTBS for Apathy in Neurocognitive Disorders","PRIME","Inclusion Criteria:\n\n* Alzheimer's disease or mixed Alzheimer's disease and vascular disease\n* MMSE score 10-28 inclusive\n* Clinically significant apathy\n* Stable dose of psychotropic medication\n* Care partner must spend at least 10hrs\u002Fweek with the participant\n\nExclusion Criteria:\n\n* Major Depressive Episode\n* Clinically significant agitation, delusions, hallucinations\n* Currently talking a dopaminergic agent other than methylphenidate\n* Failure to clear the TMS adult safety scale (e.g. unapproved pacemakers, metallic implants, history of epilepsy)\n* Central nervous system abnormalities (other than Alzheimer's disease) deemed clinically significant by study physician or seizures\n* Any condition that in the opinion of the study physician, makes it medically unsafe for the patient to enroll in the trial",{"count":250,"type":21},12,[201],"This study evaluates whether the combined treatment of methylphenidate and non-invasive brain stimulation, called intermittent theta burst stimulation, can effectively treat apathy in individuals with Alzheimer's disease or mixed AD\u002Fvascular dementia",[254,255,256,257,27,60],"Alzheimer s Disease","Alzheimer Dementia (AD)","Alzheimer Dementia","Alzheimer Disease",[63,64,259,260,261,262,263,264],"Alzheimer's disease","methylphenidate","rTMS","iTBS","repetitive transcranial magnetic stimulation","intermittent theta burst stimulation","2025-12-11",{"date":267,"type":36},"2025-12-12",{"date":269,"type":21},"2026-01",{"date":271,"type":21},"2027-10-01",{"name":273,"class":43},"Sunnybrook Health Sciences Centre",{"id":275,"slug":276,"hasResults":11,"nctId":277,"briefTitle":278,"officialTitle":279,"acronym":4,"eligibilityCriteria":280,"healthyVolunteers":11,"sex":16,"minAge":83,"maxAge":197,"enrollmentInfo":281,"targetDuration":4,"studyType":22,"phases":283,"briefSummary":284,"conditions":285,"keywords":288,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":290,"lastUpdatePostDateStruct":291,"startDateStruct":293,"completionDateStruct":295,"leadSponsor":297,"locationsCount":44},"100602088","respiratory-gated-transcutaneous-auricular-vagus-nerve-stimulation-for-improving-apathy-in-parkinsons-disease-100602088","NCT07118956","Respiratory-gated Transcutaneous Auricular Vagus Nerve Stimulation for Improving Apathy in Parkinson's Disease","Respiratory-gated Transcutaneous Auricular Vagus Nerve Stimulation for Improving Apathy in Parkinson's Disease: A Randomized, Double-blind, Sham-controlled Trial","Inclusion Criteria:\n\n1. Meet the diagnostic criteria for idiopathic Parkinson's disease (based on the MDS Clinical Diagnostic Criteria for Parkinson's Disease (2015 version)).\n2. Patients with Apathy Motivation Index (AMI) score \\>1.7.\n3. All PD patients must be on stable, standardized medication regimens with no adjustments to medications for at least 1 month prior to the study and throughout the study period.\n4. Demonstrate good compliance and adherence, capable of completing behavioral tests and taVNS therapy.\n5. Mini-Mental State Examination (MMSE) score ≥22.\n6. Meet safety criteria for MRI screening.\n\nExclusion Criteria:\n\n1. Prior brain MRI\u002FCT showing focal brain lesions or severe white matter disease (Fazekas grade 3 or higher).\n2. Secondary parkinsonism (e.g., vascular parkinsonism, drug-induced parkinsonism).\n3. History of severe traumatic brain injury, neurosurgery, or deep brain stimulation (DBS) therapy.\n4. Personal history of epilepsy, unexplained loss of consciousness, or current use of anticonvulsant medications for seizure control.\n5. Diagnosis of neuropsychiatric disorders other than Parkinson's disease.\n6. Current use of non-steroidal anti-inflammatory drugs (NSAIDs) or Non-benzodiazepine GABA receptor agonist drug or anticholinergics or corticosteroids, or history of substance abuse or drug addiction.\n7. Participation in any clinical trial within the past 3 months.\n8. Severe systemic comorbidities (e.g., hepatic\u002Frenal failure, arrhythmias, organic heart disease).\n9. Pregnant\u002Flactating women or subjects (including males) planning pregnancy within 6 months.\n10. Contraindications to taVNS, such as cardiac pacemakers, post-DBS surgery, or auricular pathologies (e.g., tympanic membrane perforation).",{"count":282,"type":21},60,[57],"The goal of this clinical trial is to learn whether 100HZ respiratory-gated vagus nerve stimulation (RAVANS) can improve the non-motor symptoms in people with Parkinson's disease (PD). It will also learn the safety of 100HZ RAVANS. The main questions it aims to answer are:\n\nCan 100HZ RAVANS improve apathy in people with PD? Did the participants have any side effects or safety issues when undergoing 100HZ RAVANS? Researchers compared 100HZ RAVANS with sham stimulation (low-dose stimulation of the same site and treatment parameters) to see if 100HZ RAVANS could improve non-motor symptoms in patients with PD.\n\nParticipants will:\n\nReceive 100HZ RAVANS or sham stimulation for 2 weeks. Neuropsychological assessment, imaging and biological sample collection were conducted before and after the entire cycle.",[143,27,286,287],"Non-motor Symptoms","Vagus Nerve Stimulation",[143,27,147,289],"Transcutaneous Auricular Vagus Nerve Stimulation","2025-11-17",{"date":292,"type":36},"2025-11-19",{"date":294,"type":36},"2025-05-01",{"date":296,"type":21},"2028-05-01",{"name":298,"class":43},"Anhui Medical University",{"id":300,"slug":301,"hasResults":11,"nctId":302,"briefTitle":303,"officialTitle":304,"acronym":4,"eligibilityCriteria":305,"healthyVolunteers":11,"sex":16,"minAge":83,"maxAge":4,"enrollmentInfo":306,"targetDuration":4,"studyType":22,"phases":308,"briefSummary":309,"conditions":310,"keywords":316,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":321,"lastUpdatePostDateStruct":322,"startDateStruct":324,"completionDateStruct":326,"leadSponsor":328,"locationsCount":44},"100601636","phase-1-accelerated-rtms-vs-sham-for-stroke-apathy-100601636","NCT07113067","Accelerated rTMS vs. Sham for Stroke Apathy","Accelerated rTMS for Post-stroke Apathy: A Double-blind Randomized Controlled Trial","Inclusion Criteria:\n\n* 40 years old or greater\n* Right- or left-hemisphere ischemic or hemorrhagic stroke with at least 6 months chronicity\n* Symptomatic apathy as confirmed by (A) total score on the Apathy Evaluation Scale by the participant or the caregiver\u002Fco-participant (AES) of ≥39\n* Ability to participate in psychometric testing and cognitive tasks\n* Intact cortex at the TMS target site as confirmed by pre-treatment MRI\n* Ability to have a co-participant\u002Fcaregiver who meets the criteria as detailed below.\n\nExclusion Criteria:\n\n* Primary extra-axial hemorrhage (subdural or subarachnoid) without ischemic stroke or intraparenchymal hemorrhage\n* Concomitant neurological disorders affecting motor or cognitive function (e.g. dementia)\n* Moderate or severe global aphasia\n* Visual impairment precluding completion of cognitive tasks\n* Presence of contraindications to MRI or TMS including electrically, magnetically or mechanically activated metal or nonmetal implants such as cardiac pacemaker, intracerebral vascular clips or any other electrically sensitive support system;\n* Pregnancy (to be later confirmed by UPT in any premenopausal female participants)\n* History of a seizure disorder\n* Preexisting scalp lesion, wound, bone defect, or hemicraniectomy\n* Claustrophobia precluding ability to undergo an MRI\n* Active substance use disorder\n* Psychotic disorders\n* Bipolar 1 Disorder\n* Acute suicidality as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)30 or suicide attempt in the previous year\n\nFor CO-PARTICIPANT\u002FCAREGIVER:\n\nInclusion Criteria:\n\n* Age 18 years or older\n* Is a reliable informant who has at least weekly contact with the participant and can speak to the participant's cognitive and everyday functioning.\n\nExclusion Criteria:\n\n\\- Unable to engage with study procedures in which Co-Participant input is needed.",{"count":307,"type":21},40,[200,201],"Apathy is a common set of symptoms seen in many people following a stroke. Apathy occurs when a person has lost motivation, becomes withdrawn, and stops doing things that used to be important to them. Apathy has a large negative impact on a person's quality of life, and can also have a large impact the people who take care of them. There are currently no FDA-approved treatments to help with apathy, and other services like therapy may be difficult to access for people who have had a stroke. To address this problem, investigators are conducting a study to find out if a form of treatment called repetitive transcranial magnetic stimulation (rTMS) can be safe and helpful for people struggling with apathy after a stroke. This study will apply a new form of rTMS which can be delivered quickly to a part of the brain called the medial prefrontal cortex (mPFC). This study will help establish whether this treatment is safe, comfortable, and effective for people with apathy after a stroke, and will help researchers develop new forms of treatment.",[27,29,311,312,313,314,315],"Stroke Sequelae","Stroke\u002FBrain Attack","Stroke\u002F Cerebrovascular Accident (Ischemic or Hemorrhagic)","Motivation","Abulia",[317,29,318,27,319,314,315,320],"Depression","Stroke Recovery","TMS","Amotivation","2025-10-21",{"date":323,"type":36},"2025-10-22",{"date":325,"type":36},"2025-08-08",{"date":327,"type":21},"2027-06-30",{"name":329,"class":43},"Medical University of South Carolina",{"id":331,"slug":332,"hasResults":11,"nctId":333,"briefTitle":334,"officialTitle":334,"acronym":4,"eligibilityCriteria":335,"healthyVolunteers":11,"sex":16,"minAge":164,"maxAge":4,"enrollmentInfo":336,"targetDuration":4,"studyType":22,"phases":338,"briefSummary":339,"conditions":340,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":321,"lastUpdatePostDateStruct":342,"startDateStruct":343,"completionDateStruct":345,"leadSponsor":347,"locationsCount":44},"100506707","targeting-network-dysfunction-in-apathy-of-late-life-depression-using-digital-therapeutics-100506707","NCT05877885","Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics","Inclusion Criteria:\n\n1. Age 60+ years\n2. Diagnosis of unipolar major depressive disorder without psychotic features, as assessed by the Mini International Neuropsychiatric Interview\n3. Montgomery-Åsberg Depression Rating Scale (MADRS) score \\> or = 16.\n4. Clinically significant apathy, determined by the Clinician-rated Apathy Evaluation Scale (C-AES \\> or = to 37)\n5. Off antidepressants or on a stable dose of an antidepressant for 8 weeks and do not intend to change the dose in the next 5 weeks.\n6. On a stable dose of other psychotropic medications, deemed by the investigator to be associated with brain networks of interest, for at least 8 weeks.\n7. Capacity to provide written consent for research assessment and treatment\n8. Ability to follow written and verbal instructions (English) as assessed by the PI and\u002For study staff.\n9. Total score of \\> 29 on the Telephone Interview for Cognitive Status (TICS)\n10. Eligible to undergo MRI\n11. Access to a computer or tablet with Wifi capabilities\n12. Able to comply with all testing and study requirements and willingness to participate in the full study duration.\n\nExclusion Criteria:\n\n1. History or presence of psychiatric diagnoses other than major depressive disorder without psychotic features, persistent depressive disorder, generalized anxiety disorder, social anxiety disorder, or specific phobia\n2. Use of cholinesterase inhibitors or psychoactive drugs other than antidepressants or benzodiazepines, including antipsychotics, that in the opinion of the Investigator may confound study data\u002Fassessments.\n3. Presence or history of significant neurologic or neurodegenerative disorder (e.g., Alzheimer's disease and other dementias, amnestic Mild Cognitive Impairment, history of stroke, Multiple Sclerosis, Parkinson's disease, epilepsy).\n4. Any other acute medical condition (e.g., cardiac, renal, or respiratory failure; severe chronic obstructive pulmonary disease; metastatic cancer; or debilitated states or less common medical illnesses) that may influence brain systems of interest or interfere with participation or interpretation of the study results.\n5. Participant is currently considered at risk for attempting suicide by the Investigator, has made a suicide attempt within the past year, or is currently demonstrating active suicidal ideation or self-injurious behavior.\n6. Electroconvulsive therapy within the past 12 months\n7. Recent history (within 6 months prior to screening\u002Fbaseline) of Substance Use Disorder.\n8. Participant is currently enrolled in ongoing concurrent cognitive rehabilitation (note that if a subject is enrolled in psychotherapy, this will not be grounds for exclusion)\n9. Claustrophobia\n10. Color Blindness\n11. Sensory or physical impairment that would preclude cognitive testing or participation in the intervention (e.g., upper limb paralysis) as reported by the participant or observed by the Investigator.\n12. Travelling consecutively for 2+ weeks during the study period to a location that will preclude timely collection of post-treatment MRI data.\n13. Contraindications to MRI scanning including cardiac pacemaker, heart valve replacement, vascular stent, cochlear implant, any other metallic biomedical implant contraindicating to MRI.",{"count":337,"type":21},84,[57],"The goal of this randomized controlled trial is to evaluate the potential of a customized digital cognitive training intervention to target aspects of brain function in apathy of late-life depression and reduce symptoms of apathy and related cognitive and behavioral deficits. The investigators hypothesize that 4 weeks of a customized digital cognitive training program will lead to changes in brain connectivity, apathy severity, and cognitive control performance.",[341,27],"Major Depressive Disorder",{"date":323,"type":36},{"date":344,"type":36},"2025-09-19",{"date":346,"type":21},"2028-12-01",{"name":348,"class":43},"AdventHealth",{"id":350,"slug":351,"hasResults":11,"nctId":352,"briefTitle":353,"officialTitle":354,"acronym":355,"eligibilityCriteria":356,"healthyVolunteers":357,"sex":16,"minAge":17,"maxAge":164,"enrollmentInfo":358,"targetDuration":4,"studyType":22,"phases":360,"briefSummary":361,"conditions":362,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":363,"lastUpdatePostDateStruct":364,"startDateStruct":366,"completionDateStruct":368,"leadSponsor":370,"locationsCount":44},"100420627","multidimensional-apathy-in-psychiatric-pathologies-100420627","NCT04757220","Multidimensional Apathy in Psychiatric Pathologies.","Cognitive and Neural Mechanisms of Multidimensional Apathy in Psychiatric Pathologies","AmSeD","Inclusion Criteria:\n\n* Inclusion criteria (all subjects):\n* age between 18 and 60 years\n* men or women volunteers, hospitalized or not\n* subject affiliated to an health insurance\n* subject having signed an informed consent\n\nInclusion criteria (for schizophrenic patients):\n\n\\- presence of DSM-V TR criteria for schizophrenia (American Psychiatric Association, 1994)\n\nInclusion criteria (for depressive patients):\n\n\\- presence of DSM-V TR criteria for depression (American Psychiatric Association, 1994)\n\nExclusion Criteria:\n\n* a major or non stabilized somatic disorder\n* medical history likely to affect cerebral anatomy or linked to an abnormality (neonatal distress, neurochirurgical intervention, neurological disorders, stroke attack)\n* any disorders involved in the use of a psycho-active substance (as defined by the DSM-IV)\n* sensory disabling impairments, and specifically visual acuity \\\u003C 8\n* general anaesthesia during the 3 months before the study\n* pregnancy (declared by the subject)\n* persons in an emergency situation\n* persons deprived in any way of their liberty\n* persons in period of exclusion in an other protocol\n\nExclusion criteria (for controls):\n\n\\- use of psychotropic substance during the 3 weeks before the study\n\nExclusion criteria (for patients):\n\n\\- use of benzodiazepines",true,{"count":359,"type":21},144,[57],"Apathy is defined by quantitative decrease in goal-directed activity in comparison to the person's previous level of functioning. Apathy is a transnosographic symptom, prevalent in many neurological and psychiatric pathologies (specifically in schizophrenia and depression), and almost half of patients suffer from it. It is an important source of burden, affecting both personal and occupational life. Despite its high prevalence and negative consequences, no pharmacological or non-pharmacological treatments exist, the underlying mechanisms of apathy being poorly understood. The main aim of the present study is to advance in our knowledge of cognitive and neural mechanisms of apathy by using a multidimensional model of apathy, distinguishing three forms: executive, emotional and auto-activation\u002Finitiative.\n\nthe investigators hypothesize, independently of the pathology (schizophrenia and depression), the existence of different cognitive deficits underlying each of the 3 subforms of apathy. Indeed, according to the predictions of Levy and Dubois' model (2006), executive disorders underlie the cognitive form of apathy. It may be related to lesions of the dorsolateral prefrontal cortex and the cognitive territory of the basal ganglia. Emotional apathy could be due to motivational disorder. Dysfunctions or lesions in the orbital and medial prefrontal cortex and limbic territories of the basal ganglia may underlie this. Finally, the initiative form, may be a mixed form, with both motivational and executive difficulties. Lesions or dysfunctions may affect both the cognitive and limbic territories of the basal ganglia or the anterior cingulate cortex.",[27],"2025-08-01",{"date":365,"type":36},"2025-08-03",{"date":367,"type":36},"2022-01-05",{"date":369,"type":21},"2027-03-01",{"name":371,"class":43},"University Hospital, Strasbourg, France",{"id":373,"slug":374,"hasResults":11,"nctId":375,"briefTitle":376,"officialTitle":377,"acronym":4,"eligibilityCriteria":378,"healthyVolunteers":11,"sex":16,"minAge":83,"maxAge":18,"enrollmentInfo":379,"targetDuration":4,"studyType":22,"phases":380,"briefSummary":381,"conditions":382,"keywords":384,"overallStatus":65,"whyStopped":4,"lastUpdateSubmitDate":391,"lastUpdatePostDateStruct":392,"startDateStruct":394,"completionDateStruct":396,"leadSponsor":398,"locationsCount":44},"100592277","vcvs-for-apathy-in-pd-100592277","NCT06991335","VC\u002FVS for Apathy in PD","Deep Brain Stimulation (DBS) of the Ventral Capsule Ventral Striatum (VC\u002FVS) for the Treatment of Apathy in Parkinson's Disease (PD)","Inclusion Criteria:\n\n* Diagnosis of Parkinson's Disorder as defined by the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (MDS-PD).\n* Presence of severe apathy as determined by apathy criteria established by the International Society for Central Nervous System Clinical Trials and Methodology Apathy Working Group (ISCTM-AWG).\n* Apathy severity of -9 to +36, on the Lille Apathy Rating Scale (LARS) for at least 2 years.\n* Documentation by primary neurologist of refractoriness to treatment for apathy with at least two dopamine-based treatments (e.g., levodopa, dopamine agonist) of sufficient dose and duration.\n* Pre-DBS neuropsychological testing indicating normal cognition. Participants with mild cognitive impairment who have been evaluated by a cognitive neurologist for consideration of treatment (i.e., cholinesterase inhibitor) if indicated, may be included in the study once treatment has been stabilized for at least 2 months.\n* Ability and willingness to give informed consent.\n* Presence of a caregiver\u002Finformant who can complete study surveys\u002Finterviews related to the study participant.\n* Stability of antidepressant medication dosing (i.e., SSRIs, Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), etc.) for a minimum of four weeks prior to surgery.\n\nExclusion Criteria:\n\n* Major neurocognitive disorder (i.e., dementia) as determined by pre-DBS neuropsychological testing.\n* Explanation of apathy symptoms by comorbid depression as determined by a psychiatric interview including the Montgomery and Asberg depression rating scale (MADRS). Individuals with a MADRS score ≥15 will be excluded.\n* History of suicide attempt in the past 36 months or current active suicidal ideation (Yes to #2-5 on the Columbia Suicide Severity Rating Scale - C-SSRS).\n* Current PD-related psychosis (e.g., visual hallucinations).\n* Any psychiatric, neurological and\u002For medical condition that makes the subject, in the opinion of the investigators, a poor candidate.\n* Alcohol\u002Fsubstance use disorder, moderate or severe, within the previous 12 months.\n* Female who is pregnant or breastfeeding or has plans to become pregnant in the next 24 months.\n* Any contraindication for MRI.\n* Presence of any of the following disorders: a) central nervous system infection, b) toxic-metabolic encephalopathy, defined as a syndrome of delirium associated with an identifiable toxin such as a chemical or metabolic disorder, c) multiple sclerosis, d) developmental delay.\n* Need for diathermy.",{"count":129,"type":21},[57],"Apathy is a disabling neuropsychiatric symptom marked by reduced goal-directed behavior, including diminished interest, motivation, emotional expression, and social engagement. Though not formally defined in the DSM-V, apathy is common in several neurological and psychiatric disorders and significantly affects quality of life. In Parkinson's Disease (PD), it affects about 40% of patients and is associated with increased caregiver burden, reduced functional ability, and nearly threefold higher mortality.\n\nPD affects over 680,000 Americans today and is projected to impact more than 1.2 million by 2030. It presents with both motor symptoms (e.g., bradykinesia, tremor, rigidity) and non-motor symptoms like depression, anxiety, and apathy. While motor symptoms are often managed with dopaminergic medications and deep brain stimulation (DBS) targeting motor regions (e.g., subthalamic nucleus, globus pallidus internal), apathy typically persists or worsens following these treatments. No FDA-approved or consistently effective treatments exist for apathy in PD. Dopamine agonists may help but have side effects that limit long-term use. SSRIs and cholinesterase inhibitors may be tried for co-occurring depression or cognitive decline, but they are not indicated for apathy and can worsen symptoms or cause adverse effects in PD.\n\nThis protocol proposes targeting apathy in PD using DBS of the ventral capsule\u002Fventral striatum (VC\u002FVS), a region involved in reward processing and goal-directed behavior. VC\u002FVS DBS is FDA-approved under a Humanitarian Device Exemption for OCD and has shown promise in treating depression, addiction, and other disorders involving motivational deficits. Neuroimaging and preclinical models strongly implicate this region in the regulation of goal-directed behavior, reward sensitivity, and cognitive control-mechanisms disrupted in apathy. Stimulating VC\u002FVS may improve motivation through fibers connected to orbitofrontal and anterior cingulate cortices (reward sensitivity) and dorsal prefrontal regions (cognitive control).\n\nSupport for this approach comes from a case report where a patient with PD and OCD received both STN and VC\u002FVS DBS. In addition to motor and OCD symptom improvement, the patient showed a significant reduction in apathy. Apathy worsened when stimulation ceased and improved again when resumed, suggesting a causal relationship. VC\u002FVS DBS was safe, did not impair motor symptoms, and appeared to enhance motivation.\n\nThis study aims to test the safety and efficacy of VC\u002FVS DBS for apathy in PD. Building on extensive animal, imaging, and clinical data, it addresses a major unmet need using an existing DBS platform. The approach is supported by established neurocircuitry, prior clinical experience with VC\u002FVS targeting, and early evidence suggesting potential benefit. It does not duplicate prior studies but extends DBS to a new, underserved indication within PD.",[143,383,27],"Deep Brain Stimulation",[385,386,63,387,388,389,390],"parkinson disease","deep brain stimulation","dbs","pd","neuromodulation","imaging","2025-05-27",{"date":393,"type":36},"2025-05-31",{"date":395,"type":21},"2025-09-01",{"date":397,"type":21},"2032-09-01",{"name":399,"class":43},"Nora Vanegas",{"id":401,"slug":402,"hasResults":11,"nctId":403,"briefTitle":404,"officialTitle":404,"acronym":405,"eligibilityCriteria":406,"healthyVolunteers":357,"sex":16,"minAge":407,"maxAge":137,"enrollmentInfo":408,"targetDuration":4,"studyType":110,"phases":4,"briefSummary":409,"conditions":410,"keywords":412,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":419,"lastUpdatePostDateStruct":420,"startDateStruct":422,"completionDateStruct":424,"leadSponsor":426,"locationsCount":44},"100586354","apathy-related-neurobehavioral-markers-of-cognitive-decline-in-old-age-bipolar-disorders-proof-of-concept-100586354","NCT06914284","Apathy-related Neurobehavioral Markers of Cognitive Decline in Old-age Bipolar Disorders: Proof-of-concept","ANACONDA","Inclusion Criteria:\n\n1. Population: Age between 70 and 85 years-old, living at home (Participants living in nursing homes are not included).\n2. Condition: OABD type 1, type 2 and type 3 assessed by the DSM5 criteria\n3. Stable: no MDE or hypomanic state within the last 6 months\n4. Ambulatory setting only\n5. General condition: Successful Gait speed test from the Short Physical Performance Battery (SPPB): beingable to walk 4 meters in 4 seconds (SPPB NIH Toolbox)44\n6. Person affiliated to a social security regime\n7. Patients who have given their free, informed and written consent to take part in the study\n\nExclusion Criteria:\n\n1. Psychiatric conditions and or co-morbidities\n\n   1. Unipolar depression\n   2. Recurrent unipolar depression\n   3. Substance use disorder according to DSM5 criteria. Benzodiaepine and\u002For z-drugs dependence are accepted.\n2. Neurological and cerebral co-morbidities\n\n   1. Major Cognitive Disorder: significant cognitive decline characterized by extensive cognitive tests or at least a standardized clinical evaluation AND at least loss of autonomy in complex instrumental daily living function, not related to delirium (DSM5 criteria)\n   2. Medical history of known degenerative disorders: Alzheimer's disease, Lobar Degenerative Fronto-temporal disorders, Lewy Body disease, corticobasal degenerative disorder, Supranuclear Palsy, epilepsy.\n   3. Medical history of known Parkinson's disease (according to the Movement Disorder Society (MDS)45 criteria)\n   4. Medical history of known stroke\n   5. Severe Parkinsonism (defined by MDS-Unified Parkinson's Disease Rating Scale46 \\> 20)\n3. MRI contra-indications: metallic implants, severe claustrophobia\n4. Adults under legal protection (safeguard of justice, curatorship, guardianship), persons deprived of their liberty.\n5. Hospitalized at inclusion","70 Years",{"count":20,"type":21},"The goal of this clinical trial is to identify reliable markers of apathy in elderly subjects with bipolar disorder, age between 70 and 85 years, in order to accurately identify subjects at high risk of progressing to dementia by measuring motor activity (actimetrics), recorded language and analysing brain changes (MRI).\n\nActimetry is the measurement and recording of body movements using an actimeter. This device is worn on the wrist and contains sensors capable of measuring and recording all movements, including those of very low intensity. An automated speech analysis using artificial intelligence is used to detect low-intensity anomalies, and we want to test whether individual differences correspond to individual differences in brain anatomy and function.\n\nResearchers will compare elderly subjects with bipolar disorder and healthy volunteer, age between 70 and 85 years.\n\nParticipants will be asked to:\n\n* Perform an MRI\n* Complete 3 cognitive tests: verbal memory, verbal fluency and an emotional storytelling task, in which you will be asked to describe a memory orally using positive, negative and neutral emotions.\n* wear an actimeter on your wrist for 4 days.",[27,411],"Bipolar Disorder",[27,413,414,415,416,417,418],"Actimetry","Neurobehavioral marker","Cognitive decline","Old Age Bipolar Disorder","MRI","Speech marker","2025-04-03",{"date":421,"type":36},"2025-04-06",{"date":423,"type":36},"2024-07-01",{"date":425,"type":21},"2029-01",{"name":427,"class":43},"Hospital Center Guillaume Régnier",{"id":429,"slug":430,"hasResults":11,"nctId":431,"briefTitle":432,"officialTitle":432,"acronym":433,"eligibilityCriteria":434,"healthyVolunteers":357,"sex":16,"minAge":17,"maxAge":83,"enrollmentInfo":435,"targetDuration":4,"studyType":22,"phases":436,"briefSummary":437,"conditions":438,"keywords":441,"overallStatus":65,"whyStopped":4,"lastUpdateSubmitDate":443,"lastUpdatePostDateStruct":444,"startDateStruct":446,"completionDateStruct":448,"leadSponsor":450,"locationsCount":4},"100569610","phase-1-effort-and-antidepressant-study-test-100569610","NCT06696482","Effort and Antidepressant Study Test","EAST","Inclusion Criteria:\n\n* Participant is willing and able to give informed consent for participation in the research\n* Aged 18 to 40 years\n* Sufficient knowledge of English language to understand and complete study tasks\n* Right-handed\n\nExclusion Criteria:\n\n* Current or past probable diagnosis of psychiatric illness, according to DSM-5 criteria requiring intervention by a healthcare professional, including but not limited to psychosis, bipolar disorder, major depression, OCD, PTSD, substance abuse disorder or any eating disorder\n* Current or past diagnosis of any significant personality disorder (e.g., borderline personality disorder) according to self-report\n* Diagnosis of attention deficit hyperactive disorder or autistic spectrum disorder that impairs daily functioning, requires pharmacotherapy or in the opinion of the study medic would affect the scientific integrity of the study\n* Current use of medication that might interact with the effects of escitalopram or affect the scientific integrity of the study\n* Previous suicide attempt or previous prolonged period (eg., \\> 5 days) of thought to end life\n* Known contraindication to escitalopram including: past allergic reaction to escitalopram or any other medicines, diagnosis of angle-closure glaucoma, or current use of any other medication whose use interacts with escitalopram (according to BNF guidance) e.g. associated with prolonged QT-interval\n* Any other current or past medical conditions which in the opinion of the study medic may interfere with the safety of the participant or the scientific integrity of the study including epilepsy\u002Fseizures, brain injury, hepatic or renal disease, diabetes, severe gastro-intestinal problems, Central Nervous System (CNS) tumours, neurobiological conditions\n* First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder\n* Severely underweight (BMI\\\u003C17) or very obese (BMI\\>40) in a manner that renders them unsuitable for the study in the opinion of the study medic\n* Heavy use of cigarettes (smoke\\>20 cigarettes per day)\n* Heavy use of caffeine (drink\\>4 x 250 ml cups\u002Fcans of coffee\u002Fenergy drinks per day)\n* Lactose intolerance (due to the study involving administration of a lactose placebo tablet)\n* Pregnancy (as determined by urine pregnancy test taken during the Part 2 screening visit), breast feeding or plans to become pregnant\n* Past history of dependence on illicit substances or regular illicit substances use within the previous three months\n* Evidence of current or past harmful use of alcohol\n* Previous participation in a study involving the tasks used in this study or involving use of escitalopram in the last year in the Department of Psychiatry (University of Oxford)\n* Physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging.\n* Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the investigator\n* Not suitable for MRI neuroimaging, e.g., difficulty remaining still for duration of scan\n* Any MRI contraindications outlined in FMRIB 3 Tesla scanning safety form",{"count":139,"type":21},[200,201],"The aim of this study is to investigate the behavioural effects and neural correlates of increasing serotonin levels in healthy volunteers, through a 7-day course of the SSRI escitalopram, on an effort-based decision-making task measuring self-benefiting and prosocial behaviours.",[439,440,27],"Effort Based Decision Making","Prosocial Behavior",[442],"fMRI","2024-11-15",{"date":445,"type":36},"2024-11-20",{"date":447,"type":21},"2025-01",{"date":449,"type":21},"2025-09",{"name":451,"class":43},"University of Oxford",{"id":453,"slug":454,"hasResults":11,"nctId":455,"briefTitle":456,"officialTitle":456,"acronym":4,"eligibilityCriteria":457,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":53,"enrollmentInfo":458,"targetDuration":4,"studyType":22,"phases":459,"briefSummary":460,"conditions":461,"keywords":464,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":468,"lastUpdatePostDateStruct":469,"startDateStruct":470,"completionDateStruct":472,"leadSponsor":473,"locationsCount":44},"100553166","phase-3-lumateperone-for-the-improvement-of-apathy-in-patients-with-psychotic-symptoms-100553166","NCT06482554","Lumateperone for the Improvement of Apathy in Patients With Psychotic Symptoms.","Inclusion Criteria:\n\n* Male or female subjects between the ages of 18-65 that have been diagnosed with Schizophrenia, Schizoaffective Disorder or Schizophrenia Spectrum and Other Psychotic Disorders.\n* A BPRS score \\> 35 at the screening visit.\n* An AES-C score \\> 32 at the screening visit.\n* If the subject is on a therapeutic regimen, that regimen must be stable for at least 30 days prior to screening. A therapeutic regimen may include medication, supplements, and\u002For probiotics.\n* In the opinion of the Investigator, the subject is able to participate in all scheduled evaluations, and likely to be compliant and complete all required assessments.\n* Female subjects of childbearing potential must not be pregnant or breast-feeding. Female subjects of childbearing potential must have a negative urine pregnancy test. Subjects of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control, which includes abstinence, while being treated on this study and for 30 days after the last dose of study drug.\n* Must speak and understand English, as the consent and all evaluations will be conducted in English.\n* Must be willing to take and pass a urine drug screen with a negative result in order to rule out psychotic symptoms due to drugs of abuse.\n\nExclusion Criteria:\n\n* A BPRS score \\\u003C 35 at the screening visit.\n* An AES-C score \\\u003C 32 at the screening visit.\n* Have any clinically significant medical condition or an unstable intercurrent illness that would, in the opinion of the Investigator, preclude study participation.\n* Are currently taking more than one antipsychotic medication.\n* Are currently taking a long-acting injectable medication for psychotic symptoms.\n* Have a substance use disorder or show a positive drug screen for stimulants.\n* Are pregnant or of female sex with no evidence of measures for pregnancy prevention.\n* Presence of dementia.\n* Intellectual disability or cognitive impairment that would affect the symptom\u002Fapathy assessments, in the view of the investigator.\n* A diagnosis of Parkinson's disease.",{"count":166,"type":21},[24],"This study is looking to determine if Lumateperone improves motivation in patients with schizophrenia or schizoaffective disorders who show high levels of apathy as judged by AES-C-Apathy (Apathy Evaluation Scale - Clinician - Apathy) assessment and to examine a possible correlation between improvement in apathy scores and changes in elements of the PANSS (Positive and Negative Syndrome Scale) due to treatment with Lumateperone.",[27,462,463],"Schizophrenia","Schizophrenia; Psychosis",[462,465,466,467],"Schizoaffective","Psychosis","Psychotic","2024-06-26",{"date":423,"type":36},{"date":471,"type":21},"2024-06",{"date":184,"type":21},{"name":474,"class":43},"Louisiana State University Health Sciences Center Shreveport",{"id":476,"slug":477,"hasResults":11,"nctId":478,"briefTitle":479,"officialTitle":479,"acronym":480,"eligibilityCriteria":481,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":407,"enrollmentInfo":482,"targetDuration":4,"studyType":22,"phases":484,"briefSummary":485,"conditions":486,"keywords":4,"overallStatus":65,"whyStopped":4,"lastUpdateSubmitDate":490,"lastUpdatePostDateStruct":491,"startDateStruct":493,"completionDateStruct":495,"leadSponsor":497,"locationsCount":4},"100530237","stratifying-psychoses-for-personalized-repetitive-tms-in-persistent-negative-symptoms-alleviation-100530237","NCT06184165","Stratifying Psychoses for Personalized REpetitive TMS in Persistent NEgative Symptoms Alleviation","SP-RENESA","Inclusion Criteria:\n\n* 18-70 years of age; affiliated to health insurance; superior or equal to B2 level of linguistic competency in French.\n* Suffering from schizophrenia spectrum disorder (SSD) in residual state with persistent negative symptoms (PNS): (1) SSD: ICD-11 codes beginning with 6A2 + primary catatonia (codes beginning with 6A4) + simple schizophrenia as defined in ICD-10 (F20.6); (2) PNS: persistence (≥6 months - based on patient ± informant's interview) of ≥2 negative symptoms (PANSS-N1, N2, N3, N4, N6 ≥4) with functional impact.\n* Half of subjects having PPC, the other half suffering from another phenotype or nPPC (neuropsychiatric procedure or probabilistic, i.e. Bayes-PPC).\n* Under a stable medication regimen for \\>6 weeks,\n* Subjects who have received the protocol information and signed informed consent.\n\nExclusion Criteria:\n\n* \\- Contraindications for MRI or rTMS.\n* Motor deficit at neurological examination.\n* Secondary negative symptoms: (1) withdrawal secondary to severe anxiety (especially due to positive symptoms), (2) depression, (3) maintenance on high dose antipsychotics, (4) extra-pyramidal or (5) sedation side-effects, (6) treatment non-compliance, (7) current substance abuse (except nicotine and caffeine), (8) unsubstituted past opioid addiction, (9) poor health or social condition.\n* Under antiepileptic drugs (except lamotrigine and long-term use of benzodiazepines).\n* Pregnancy; severe medical condition; care under constraint.",{"count":483,"type":21},160,[57],"In its 2012's release guideline on therapy for schizophrenia, the EMA joined the FDA to acknowledge primary and persistent negative symptoms (PNS) as an unmet need in the treatment of schizophrenia. Functional brain imaging studies showed a correlation between NS and reduced perfusion in the left dorsolateral prefrontal cortex (L-DLPFC). Pre-frontal activation (PFA) using repetitive transcranial magnetic stimulation (rTMS) significantly improve PNS (meta-analyses: effect size SMD = 0.55, ΔPANSS-N = -2.5). Yet schizophrenia is likely to gather many different natural entities of distinct pathophysiological mechanisms. Pursuing a one-size-fits-all approach will not adapt to this diversity and might account for inconsistencies in the results.\n\nProgressive periodic catatonia (PPC) is a rare psychotic phenotype (0.1 - 0.5 ‰) which has been shown to be longitudinally stable (30-years follow-up) and consistent within families (about 1 third of first-degree relatives are affected). The core of this phenotype is a disintegration of psychomotor processes which progresses with each relapse, resulting in a \"deficit state\", i.e., PNS, responsible for most social and occupational disabilities. The investigators and others reported PPC to come with hyper-perfusions in premotor cortices compared to controls or non-PPC chronic psychoses (nPPC). These hyper-perfusions discriminate PPC from nPPC or depressive patients (Sensitivity = 82%; Specificity = 95%). Last, in independent proof-of-principle studies the investigators and others have shown that premotor inhibition (PMI) using rTMS significantly improved PNS in PPC and that the most dramatic improvements followed personalized accelerated rTMS protocols (5 days of rTMS; CGI-improvement = 2 which is equivalent to ΔPANSS-N = -10; lasting \\> 1 month - vs virtually no change for PFA). The efficacy index was very good (no side effects).\n\nthe investigators hypothesize that: (1) in PPC, add-on personalized premotor inhibition (PMI) is more effective in reducing PNS than L-DLPFC activation (PFA); (2) patient stratification is relevant as personalized PMI will not be as effective in the nPPC group (even expected to be less effective than PFA).",[462,487,488,489,27],"Persistent Negative Symptoms","Progressive Periodic Catatonia","Aviation","2023-12-14",{"date":492,"type":36},"2023-12-28",{"date":494,"type":21},"2024-03-01",{"date":496,"type":21},"2028-11-01",{"name":371,"class":43},{"id":499,"slug":500,"hasResults":11,"nctId":501,"briefTitle":502,"officialTitle":503,"acronym":504,"eligibilityCriteria":505,"healthyVolunteers":11,"sex":16,"minAge":83,"maxAge":4,"enrollmentInfo":506,"targetDuration":4,"studyType":22,"phases":507,"briefSummary":508,"conditions":509,"keywords":510,"overallStatus":65,"whyStopped":4,"lastUpdateSubmitDate":512,"lastUpdatePostDateStruct":513,"startDateStruct":515,"completionDateStruct":517,"leadSponsor":519,"locationsCount":4},"100490672","phase-2-methylphenidate-for-apathy-in-veterans-with-parkinsons-disease-100490672","NCT05669170","Methylphenidate for Apathy in Veterans With Parkinson's Disease","Evaluating Safety and Potential Benefit of Methylphenidate as a Symptomatic Treatment for Apathy in Veterans With Parkinson's Disease.","MAV-PD","Inclusion Criteria:\n\n* • Clinically established or probable Parkinson disease according to the Movement Disorders Society Clinical Diagnostic Criteria for Parkinson's Disease\n\n  * Age 40 or older at the time of screening\n  * Montreal Cognitive Assessment (MoCA) score between 17-30.\n  * Clinical Dementia Rating scale (CDR) lower than 1 and CDR sum of boxes lower than 4.5. The CDR is a numeric scale used to quantify the severity of symptoms of dementia. Using a structured interview protocol, qualified raters assess the subject's cognitive and functional performance in six areas: memory, orientation, judgement, and problem solving, community affairs, home and hobbies, and personal care. Scores are combined to obtain a composite score ranging from 0 through 3. A score between 0 and 1 indicates none or mild symptoms. The individual scores can also be added up, which gives the sum of boxes score.\n  * Clinically significant apathy for at least four weeks for which either the frequency of apathy as assessed by the Neuropsychiatric Inventory (NPI) is 'Very frequently', or the frequency of apathy as assessed by the NPI is 'Frequently' or 'Often' AND the severity of apathy as assessed by the NPI is 'Moderate' or 'Marked'\n  * Provision of informed consent for participation in the study by the patient. The ability to provide consent will be determined by the Assessment of Capacity for Everyday Decision-Making (ACED). The total score must be 9 (out of 10) or higher to meet the criteria for the study.\n  * Availability of primary caregiver, who spends greater than ten hours a week with the patient and supervises his\u002Fher care, to accompany the patient to study visits and to participate in the study\n  * Sufficient fluency of both the patient and caregiver in written and spoken English\n  * No change to PD medications within the month preceding randomization, including starting, stopping, or dosage modifications\n  * Treatment with stable doses of levodopa and cholinesterase inhibitors (ChEIs) is allowable if stable for 3 months before randomization. Other psychotropics (with the exclusion of antipsychotics), if stable for 3 months, may be allowed only with PIs' approval on a case-by-case basis\n\nExclusion Criteria:\n\n* • Meets criteria Major Depressive Episode according to the Diagnostic Statistical Manual of Mental Disorder 5\n\n  * History of psychotic symptoms due to another illness (i.e., schizophrenia, psychosis in mood disorders, etc.) in the past 2 years\n  * Clinically significant agitation\u002Faggression for which either the frequency of agitation\u002Faggression as assessed by the NPI is 'Very frequently', or the frequency of agitation\u002Faggression as assessed by the NPI is 'Frequently' AND the severity of the agitation as assessed by the NPI is 'Moderate', or 'Marked'\n  * Clinically significant delusions for which either the frequency of delusions as assessed by the NPI is 'Very frequently', or the frequency of delusions as assessed by the NPI is 'Frequently' AND the severity of the delusions as assessed by the NPI is 'Moderate', or 'Marked'\n  * Clinically significant hallucinations for which either the frequency of hallucinations as assessed by the NPI is 'Very frequently', or the frequency of hallucinations as assessed by the NPI is 'Frequently' AND the severity of the hallucinations as assessed by the NPI is 'Moderate', or 'Marked'\n  * Clinically significant impulse control disorders as assessed by the QUIP\n  * Substance use disorder in the past year as assessed by the Drug Abuse Screening Test (DAST-10).\n  * Treatment with psychotropic medications in the 2 weeks prior to randomization with the exception of approved treatments for cognitive impairment (ChEIs and memantine), selective serotonin reuptake inhibitor antidepressants, and trazodone (if used as an aid to facilitate sleep and not as an antidepressant); other psychotropics (with the exclusion of antipsychotics), if stable for 3 months, may be allowed only with PI approval on a case-by-case basis. Note that antipsychotics are expressly prohibited\n  * Treatment with methylphenidate is contraindicated in the opinion of the PIs\n  * Failure of treatment with methylphenidate in the past for apathy\n  * Treatment with a medication that would prohibit the safe concurrent use of methylphenidate such as monoamine oxidase inhibitors and tricyclic antidepressants\n  * Need for acute psychiatric hospitalization\n  * Active suicidal ideation as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS).60 If any of the responses to the questionnaires are yes, the subject will be evaluated by a psychiatrist to assess the risk of suicidality.\n  * Uncontrolled hypertension (medication non-compliance or past 3 months with a diastolic reading of 105 mmHg)\n  * Symptomatic coronary artery disease deemed to be significant by the PIs at the time of screening\n  * Unintentional weight loss as determined by the PIs in the last three months\n  * Significant communicative impairments that prohibit meaningful participation in the study assessments\n  * Current participation in a clinical trial\n  * Hyperthyroidism, advanced arteriosclerosis, symptomatic cardiovascular disease, serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or a family history of sudden death or death related to heart problems\n  * Glaucoma, pheochromocytoma, or known or suspected hypersensitivity to methylphenidate or its excipients\n  * CNS abnormalities (e.g., cerebral aneurysm) and\u002For other vascular abnormalities such as vasculitis or pre-existing stroke, motor tics or family history or diagnosis of Tourette's syndrome, seizures (convulsions, epilepsy), or abnormal EEGs\n  * Any condition that, in the opinion of the PIs, makes it medically inappropriate or risky for the patient to enroll in the trial\n  * Women who are currently pregnant (methylphenidate is category D). Screening will include pregnancy test",{"count":282,"type":21},[201],"Apathy is one of the most common behavioral symptoms of Parkinson's disease. Patients with apathy show diminution in motivation and goal-directed behaviors, which is a fundamental aspect of human functioning, affecting dependency and quality of life. Although apathy is thought to be potentially treatable currently there are no effective treatments for apathy. Given the higher incidence of medical and psychiatric comorbidities, the Veterans Affairs health system represents a unique population for which medication response may be different from the general population. This study aims to evaluate if a medication that has already been proven to be useful in Alzheimer's disease patients with apathy, could be helpful in Parkinson's disease as well as decreasing its debilitating consequences and reducing patients' dependency on caregivers, providing well-deserved relief to patients and their loved ones.",[143,27],[260,63,511],"Parkinson disease","2022-12-28",{"date":514,"type":36},"2022-12-30",{"date":516,"type":21},"2024-01",{"date":518,"type":21},"2028-06",{"name":520,"class":521},"Ralph H. Johnson VA Medical Center","FED"]