[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Laureate Institute for Brain Research, Inc.\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":305},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,12,0,[8,42,64,92,111,135,166,187,217,240,261,282],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":15,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":36,"leadSponsor":38,"locationsCount":41},"100420176","phase-1-neural-response-to-inflammatory-challenge-in-major-depressive-disorder-100420176",false,"NCT04751331","Neural Response to Inflammatory Challenge in Major Depressive Disorder","Inclusion Criteria:\n\nBoth healthy controls and depressed participants will be required to be in good general health (as evaluated during Visit 1, including EKG) and to be 18-65 years of age. A DSM-V diagnosis of MDD will be made with the MINI International Neuropsychiatric Interview and current symptoms of depression will be measured with the clinician-administered MADRS and the self-report PHQ-9. Depressed participants will be required to have symptoms of depression (i.e. a PHQ-9 score ≥10) and\u002For a MADRS score of ≥7.\n\nExclusion Criteria:\n\nGeneral Exclusion Criteria:\n\n* Pregnancy\n* A history of fainting during blood draws will be evaluated by the clinical team and may be deemed exclusionary.\n\nMedical Conditions:\n\n* Moderate to severe traumatic brain injury (\\>30 min. loss of consciousness or \\>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits.\n* Presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders.\n* Presence of co-morbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders.\n* Presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or to put the study participant at undue risk.\n* Presence of chronic infection that may elevate pro-inflammatory cytokines.\n* Presence of an acute infectious illness or receipt of a vaccination in the two weeks prior to an experimental session.\n\nPsychiatric Disorders:\n\n* Current severe suicidal ideation or attempt within the past 12 months.\n* Psychosis\n* Bipolar disorder\n* Substance abuse or dependence within the previous 6 months\n\nContraindications for MRI:\n\n* Cardiac pacemaker, metal fragments in eyes\u002Fskin\u002Fbody (shrapnel), aortic\u002Faneurysm clips, prosthesis, by-pass surgery\u002Fcoronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates\u002Fpins\u002Fscrews\u002Fwires, or neuro\u002Fbio-stimulators (TENS unit), persons who have ever been a professional metal worker\u002Fwelder, history of eye surgery\u002Feyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy.\n* Claustrophobia that is severe enough to preclude MRI scanning.\n\nMedications:\n\n* Current and\u002For past regular use of hormone-containing medications (excluding contraceptives)\n* Use of medications such as oral corticosteroids which may have immunosuppressive effects.\n* Current use of non-steroid anti-inflammatory drugs that is deemed by the investigators to potentially confound the results of the study (e.g. \\> 3 days\u002Fweek)\n* Current and\u002For past regular use of immune modifying drugs that target specific immune responses such as TNF antagonists\n* Current use of analgesics such as opioids or history of addiction to opioids or other analgesics\n* Current and\u002For past regular use of cardiovascular medications, including antihypertensive, antiarrhythmic, anti-anginal, and anticoagulant drugs (does not apply where medications are taken for different purpose e.g. anti-hypertensives for migraine).\n* Chronic use of antibiotics such as isotretinoin or minocycline because of their potential effects on the microbiome and immune function.\n* Evidence of recreational drug use from urine test.\n* Lifetime use of methamphetamine\n* Inclusion of individuals reporting other types of medications or supplements not listed or considered thus far will be at the discretion of the PI based on their potential to affect immune function, the microbiome, brain function or brain blood flow.\n\nHealth Factors:\n\n* BMI \\> 35 because of the effects of obesity on pro-inflammatory cytokine activity\n* Clinically significant abnormalities on screening laboratory tests\n* Abnormal EKG\n* In addition, participants who on arrival to the study, show any of the following symptoms will not be allowed to complete the study:\n\n  1. screening supine systolic blood pressure \\>140 mmHg or \\\u003C100 mmHg\n  2. screening supine diastolic blood pressure \\>90 mmHg or \\\u003C60 mmHg\n  3. 12-lead EKG demonstrating a PR interval \\> 0.2 msec QTc \\>450 or QRS \\>120 msec (Bazett) If the QTc exceeds 450 msec, or QRS exceeds 120 msec, the EKG will be repeated 2 more times and the median value will be used\n  4. pulse less than 50 beats\u002Fminute or greater than 100 beats\u002Fminute\n  5. temperature greater than 99.5 degrees F.\n\n     Non-English speaking participants:\n* The majority of the assessments proposed for this study have not been translated from English, thus, non-English speaking volunteers will be excluded.",true,"ALL","18 Years","65 Years",{"count":20,"type":21},180,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","This is a parallel group, double-blinded, placebo-controlled study. Participants with MDD (n=90) and HC (n=90) will be randomly assigned (2:1) to receive either lipopolysaccharide (LPS) (0.8ng\u002Fkg of body weight) or placebo (same volume of 0.9% saline) administered as an intravenous bolus. This will yield the following groups: MDD-LPS (n=60), MDD-Placebo (n=30), HC-LPS (n=60), HC-placebo (n=30).\n\nThere are three main aims: to identify immune pathways and neural circuits that respond differently to LPS in MDD vs. HC subjects; (2) to test whether the strength of inflammatory changes induced by LPS is associated with degree of change in anhedonic symptoms and neural circuits in the MDD group, and (3) to identify a biotype of MDD that shows a differential immunological and neurophysiological response to LPS. The main outcome variables are symptoms of anhedonia measured with the Snaith-Hamilton Pleasure Scale (SHAPS), cytokines (Il-6, IL-8, IL-10, and TNF), and BOLD signal change in the neural circuitry mediating interoceptive processing, i.e. the insula and cingulate cortex. The exploratory aim is to determine whether the acute inflammatory response to LPS can predict the clinical course of depression over a period of six months. The main outcome of this component of the study is self-reported depressive symptoms assessed with the QIDS-SR.",[28],"Major Depressive Disorder","RECRUITING","2026-04-16",{"date":32,"type":33},"2026-04-21","ACTUAL",{"date":35,"type":33},"2021-05-15",{"date":37,"type":21},"2026-12",{"name":39,"class":40},"Laureate Institute for Brain Research, Inc.","OTHER",1,{"id":43,"slug":44,"hasResults":11,"nctId":45,"briefTitle":46,"officialTitle":47,"acronym":4,"eligibilityCriteria":48,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":49,"targetDuration":4,"studyType":22,"phases":51,"briefSummary":53,"conditions":54,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":56,"lastUpdatePostDateStruct":57,"startDateStruct":59,"completionDateStruct":61,"leadSponsor":63,"locationsCount":41},"100605560","lifu-mechanisms-for-ptsd-in-healthcare-workers-100605560","NCT07164105","LIFU Mechanisms for PTSD in Healthcare Workers","Mechanisms of Low Intensity Focused Ultrasound of the Ventral Anterior Cingulate Cortex for Post-Traumatic Stress Disorder in Frontline Healthcare Workers","Inclusion Criteria:\n\n1. Adults in a frontline healthcare position (e.g. emergency medical services)\n2. Ages 18-65 years\n3. PTSD Checklist for DSM-5 (PCL-5) score ≥ 33 and \\\u003C 65, OR at least partial PTSD as measured by the MINI\n4. English proficiency as evaluated by language ability during screening\n\nExclusion Criteria:\n\n1. Neurological disorders\n2. DSM-5 diagnosis of psychotic disorders, eating disorder, obsessive-compulsive disorder, moderate to severe alcohol or substance use disorder within the past year, bipolar disorder, or major depressive disorder with psychosis\n3. Suicidal intent or plan (as measured by Suicide-Risk-Assessment-C-SSRS \"Yes\" answers to items 3, 4 or 5 of Suicidal Ideation-Past 1 month section, or any \"Yes\" answer to any of the items of Suicidal Behavior-Past 3 months section), or any suicide attempt in the last 3 months.\n4. History of severe traumatic brain injury (as indicated by score ≥ 3 on the Tulsa Head Injury Screen) or of skull fractures\n5. Contraindications to MRI as determined by the MR Environment Screening\n6. Pregnancy, determined by urine pregnancy test administered prior to every MRI scanning procedure\n7. Evidence of inability to comply with study procedures based on experimenter judgement.\n8. Change in the dose or prescription of a medication within the 6 weeks before enrolling in the study that could affect brain functioning, e.g., anxiolytics, antipsychotics, antidepressants, benzodiazepines, or mood stabilizers.\n9. Non-correctable vision or hearing problems\n10. Unstable medical diagnoses\n11. Any structural abnormalities in the LIFU target region on screening brain MRI.",{"count":50,"type":21},66,[52],"NA","The goal of this clinical trial is to evaluate whether low-intensity focused ultrasound (LIFU) of the ventral anterior cingulate cortex (vACC) can normalize dysfunctional brain activation patterns and behaviors in frontline healthcare workers with post-traumatic stress disorder. The main questions it aims to answer are:\n\n* Does LIFU of the vACC effect activity and connectivity of the vACC and amygdala?\n* Does LIFU of the vACC reduce post-traumatic stress symptoms? Researchers will compare LIFU to sham modulation to see if LIFU modulates activity of vACC-amygdala circuitry and affects threat sensitivity and emotion regulation.\n\nParticipants will:\n\n* Complete two fMRI sessions (before and after LIFU)\n* Receive a single session of LIFU or sham modulation of the vACC\n* Wear a wearable device that tracks sleep and heart rate metrics",[55],"PTSD and Trauma-related Symptoms","2026-04-15",{"date":58,"type":33},"2026-04-20",{"date":60,"type":33},"2025-12-29",{"date":62,"type":21},"2028-08",{"name":39,"class":40},{"id":65,"slug":66,"hasResults":11,"nctId":67,"briefTitle":68,"officialTitle":69,"acronym":4,"eligibilityCriteria":70,"healthyVolunteers":15,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":71,"targetDuration":4,"studyType":22,"phases":73,"briefSummary":74,"conditions":75,"keywords":78,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":56,"lastUpdatePostDateStruct":85,"startDateStruct":87,"completionDateStruct":89,"leadSponsor":91,"locationsCount":41},"100609998","decoding-emotional-dynamics-in-bipolar-disorder-100609998","NCT07221864","Decoding Emotional Dynamics in Bipolar Disorder","Decoding Emotional Dynamics Driving Mood Instability in Bipolar Disorder","Inclusion Criteria\n\n1. Age 18 to 65 years\n2. Male or female\n3. BMI between 18.5 and 38.0 kg\u002Fm2 at Screening\n4. Capable of understanding and complying with study requirements\n5. Fluent in English\n6. Able to provide informed consent\n\n   BD Group:\n7. Meet the DSM-5 diagnostic criteria for BD-I or BD-II who are currently depressed or mixed state defined by the Mini-International Neuropsychiatric Interview (MINI)\n8. Moderate or greater depressive symptom severity (MADRS ≥ 15 or PHQ-9 ≥ 10)\n\n   HC Group:\n9. No current or past psychiatric disorder (verified by MINI)\n\nExclusion Criteria\n\n1. No telephone or easy access to a telephone\n2. Significant medical problems as identified by the medical screening questionnaire: e.g. a history of unstable liver or renal insufficiency; glaucoma; significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbance; or any other condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the participant or that could prevent, limit, or confound the protocol-specified assessments\n3. A positive test for drugs of abuse, including alcohol (breath test), cocaine, opiates, amphetamines, methamphetamines, phencyclidine, benzodiazepines, barbiturates, methadone, and oxycodone\n4. Drug or alcohol intoxication (based on positive UTOX or breathalyzer test at screening or study session) or reported alcohol\u002Fdrug withdrawal, last cannabis use must be \\>48 hours prior to study session.\n5. Current DSM-5 diagnosis of a psychosis spectrum disorder or moderate to severe substance use disorder\n6. Moderate to severe traumatic brain injury or other neurocognitive disorder with evidence of neurological deficits, neurological disorders, or severe or unstable medical conditions that might be compromised by participation in the study (to be determined by primary care provider)\n7. Current significant suicidal ideation or suicide attempt within the past 3 months.\n8. Change in the dose or prescription of a medication within the 6 weeks before enrolling in the study that could affect brain functioning, e.g., anxiolytics, antipsychotics, antidepressants, or mood stabilizers\n9. Taking drugs that affect the fMRI hemodynamic response (e.g., methylphenidate, acetazolamide, excessive caffeine intake \\> 1000 mg\u002Fday)\n10. MRI contraindications as documented on the MR Environment Screening\n11. Unwillingness or inability to complete any of the major aspects of the study protocol, including magnetic resonance imaging (i.e., due to claustrophobia), or behavioral assessment. However, failing to complete some individual aspects of these assessment sessions will be acceptable (i.e., being unwilling to answer individual items on some questionnaires or being unwilling to complete a behavioral task)\n12. Non-correctable vision or hearing problems",{"count":72,"type":21},72,[52],"The goal of this neuroimaging study is to investigate how emotional states fluctuate in people with bipolar disorder (BD) compared to healthy controls, and to understand the neural mechanisms driving mood instability. The main questions it aims to answer are:\n\n* Can emotional states be decoded from fMRI brain activity using machine learning?\n* Do individuals with BD show more unstable emotional state trajectories (e.g., high metastability, low fractal scaling) than healthy controls?\n* Does amplifying positive emotions stabilize brain and emotional dynamics in BD?\n\nResearchers will compare individuals with bipolar disorder (BD-I or BD-II, currently depressed or mixed state) to healthy controls without psychiatric history to see whether the BD group shows greater fluctuations in emotional brain activity and whether positive emotion regulation strategies normalize this instability.\n\nParticipants will:\n\n* Complete self-report questionnaires on mood, emotion regulation, anxiety, and daily functioning.\n* Recall and provide short descriptions of personal positive and negative memories to be used in the MRI task.\n* Undergo fMRI scanning, including:\n* Resting-state scans\n* A Think and Regulate Affective States Task (TReAT) where they recall autobiographical memories, rate emotions, and practice amplifying positive mood.\n* Structural and diffusion MRI for brain mapping.\n* Receive physiological monitoring (heart rate, respiration) during scanning.\n* Complete post-scan surveys on emotional state and task experience.\n\nThis research will help clarify how the brain supports or disrupts emotional regulation in bipolar disorder and may inform the development of personalized, neurobiologically informed treatments for mood instability.",[76,77],"Bipolar Disorder I or II","Healthy (Controls)",[79,80,81,82,83,84],"neuroimaging","fMRI","Bipolar Disorder I","Bipolar Disorder II","machine learning","emotion regulation",{"date":86,"type":33},"2026-04-17",{"date":88,"type":33},"2025-10-30",{"date":90,"type":21},"2028-11",{"name":39,"class":40},{"id":93,"slug":94,"hasResults":11,"nctId":95,"briefTitle":96,"officialTitle":97,"acronym":4,"eligibilityCriteria":98,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":99,"targetDuration":4,"studyType":22,"phases":101,"briefSummary":102,"conditions":103,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":56,"lastUpdatePostDateStruct":105,"startDateStruct":106,"completionDateStruct":108,"leadSponsor":110,"locationsCount":41},"100536348","phase-2-evaluation-of-a-keto-like-supplement-on-brain-responses-to-emotional-stimuli-in-depression-100536348","NCT06263660","Evaluation of a Keto-Like Supplement on Brain Responses to Emotional Stimuli in Depression","Exploratory Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Effect of a Keto-Like Supplement in Depressed Patients on Functional Brain Responses to Positive and Negative Stimuli","Inclusion Criteria:\n\n* Meets the Diagnostic and statistical manual - 5 (DSM-5) diagnostic criteria for MDD without psychotic features (past or present), as confirmed by the M.I.N.I v7.0\n* PHQ-9 score of ≥10\n* C-Reactive Protein (CRP) value \\> 1\n* Age 18-65\n* Consent ability and written consent\n* Body Mass Index (BMI) between 19 and 38 kg\u002Fm2\n* Medically stable based on clinical laboratory tests, medical history and vital signs\n* No intention to become pregnant during the study\n* A woman of childbearing potential must have a negative serum pregnancy test at screening\n* Consent that possible random finding is reported (e.g. brain abnormality during imaging)\n\nExclusion Criteria:\n\n* Has a current or recent history of clinically significant suicidality\n* Has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 12 months before screening\n* Has positive test result(s) for alcohol or drugs of abuse (including methadone, opiates, cocaine, cannabinoids, amphetamine\u002Fmethamphetamine and ecstasy)\n* Has a current diagnosis of a psychotic disorder (e.g. schizophrenia, bipolar disorder), an eating disorder (e.g. anorexia, bulimia), or learning disability or a personality disorder that is considered by the investigator to interfere with the ability of the subject to adhere to the protocol (e.g. narcissistic personality, borderline personality disorder)\n* Change in medication dose and\u002For frequency within the last 6 weeks. Participants must be on stable medications for 6 weeks prior to enrollment.\n* Plans to change medication dose\u002Ffrequency during the course of the study. Must plan to remain on stable dose for the duration of the study, unless otherwise indicated by their provider during the course of the study.\n* Plans to take vitamins and\u002For mineral supplements during the study. Must refrain for the duration of the study\n* Unable to complete MRI scans\n* Is a woman who is pregnant or breast feeding\n* Plans to conceive a child while enrolled in this study or within 3 months after the last dose of the keto-like supplement\n* Has received an investigational drug\u002Fvaccines, used an invasive investigational medical device within 60 days before the planned first dose of the keto-like supplement or has participated in 2 or more interventional clinical studies in the previous 1 year, or is currently enrolled in any drug or non-drug interventional study.\n* Has had major surgery, (i.e. requiring general anesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time they are expected to participate in the study.\n* Intake of Omega 3 fatty acids (DHA, EPA, fish oil supplements)\n* Significant cognitive impairment, clinically relevant or progressive disease (e.g., liver, kidney, cardiovascular system, respiratory tract, vascular system, brain, metabolism, thyroid) that could affect the course of the study\n* Known metabolic disorders (e.g., fatty acid oxidation disorders, ketolysis\u002Fketogenesis or glucogenesis disorder, hyperinsulinism (e.g., pancreatic neuroendocrine tumor), pyruvate carboxylase deficiency, Type 1 and Type 2 diabetes\n* Allergy to Stevia sweetener, malic acid or orange flavoring\n* Concern for inability to maintain adherence to the keto-like supplement administration protocol\n* Currently practicing a ketogenic or paleo diet or planning to do so during the study period.\n* Change in body weight of more than 5 kg within one month before the start of the intervention\n* Medical, psychiatric or other conditions that restrict the patient's following abilities: to interpret the study information, to give informed consent, to adhere to the rules of the protocol, or to complete the study\n* Contraindications to MRI examinations \\[persons with metallic implants (e.g., intracranial metal clips) and carriers of electronic devices (e.g., pacemaker) or persons with claustrophobia\\]",{"count":100,"type":21},75,[25],"This study aims to determine whether a keto-like supplement relative to placebo results in functional brain changes during fMRI tasks evaluating positive and negative valence in individuals with moderate to severe depression. In this double-blind randomized placebo-controlled trial, 75 individuals with a Patient Health Questionnaire (PHQ-9) scale score ≥ 10 (MDD) will be enrolled to participate in an 8-week treatment study to obtain 60 completers. Participants will be randomized with a 1-1 ratio to receive the keto-like supplement (n= 30 completers) or placebo (n=30 completers) taken orally three times per day for 8 weeks. Participants will undergo a 10.5-hour screening\u002Fbaseline evaluation visit split over 2 days at week 0 including questionnaires, neuroimaging before and after supplement or placebo administration and blood draws, office visits at week 2 (1.5 hours), week 4 (3 hours), week 6 (0.5 hours), week 8 (6 hours), a follow-up visit at week 10 (1.5 hours) and two phone calls between visits (weeks 1 and 3) during which a brief clinical assessment will be obtained (10 minutes each). The total time involved in the study is approximately 23.5 hours.",[104],"Depression",{"date":58,"type":33},{"date":107,"type":33},"2024-01-09",{"date":109,"type":21},"2027-12",{"name":39,"class":40},{"id":112,"slug":113,"hasResults":11,"nctId":114,"briefTitle":115,"officialTitle":116,"acronym":117,"eligibilityCriteria":118,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":119,"targetDuration":4,"studyType":22,"phases":121,"briefSummary":122,"conditions":123,"keywords":125,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":127,"lastUpdatePostDateStruct":128,"startDateStruct":130,"completionDateStruct":132,"leadSponsor":134,"locationsCount":41},"100605728","ultrasound-neuromodulation-of-circuits-and-negative-valence-systems-in-treatment-resistant-depression-100605728","NCT07166289","Ultrasound Neuromodulation of Circuits and Negative Valence Systems in Treatment-Resistant Depression","Parsing Mechanistic Relationships Between Circuits and Negative Valence System Behaviors in Treatment-Resistant Depression With Ultrasound Neuromodulation","LIFU CANVAS","Inclusion Criteria:\n\n1. Persons 18-65 years old, with sex and ethnicity recruitment targets including a M:F proportion of 1:2 and White:Black:Hispanic:Native American proportion as close as possible to 8:2:2:1 to reflect the regional epidemiology of TRD (63% White American; 16% African American; 14% Hispanic of any race; 5% Native American),\n2. DSM-5-TR diagnosis of MDD as confirmed by MINI structured interview followed by consultation with a board-certified psychiatrist,\n3. Evidence of treatment resistance defined as continued MDD symptoms despite any of the following:\n\n   1. two or more adequate (6 week) trials of antidepressants with different mechanisms,\n   2. evidence-based psychotherapy,\n   3. augmentation agent (lithium, atypical antipsychotic, or T3), or\n   4. consideration of ECT or prior ECT nonresponse or intolerance,\n4. at least moderate symptoms as indicated by MADRS≥20 upon screening\n5. stable treatments including psychotherapy and medication for at least six weeks prior to participation.\n6. Fluent English speaker, capable of written consent\n7. Consent that random observations of pathology are possible (e.g., brain abnormality seen during imaging)\n\nExclusion Criteria:\n\n1. Clinical history of at least minor neurocognitive disorder of neurodegenerative origin,\n2. PROMIS (Cognitive Function scale) score ≤40 (i.e., mean - 1SD), collected at baseline\n3. clinical history of relevant structural pathology of the central nervous system, including Parkinson's disease, multiple sclerosis, and brain malignant neoplasia,\n4. uncontrolled diabetes mellitus (as evidenced by a fasting glycemia ≥ 120 mg\u002FdL or hemoglobin A1c ≥ 6.5%) or hypertension (as evidenced by two consecutive readings ≥ 140\u002F90 mmHg) to ensure medical stability, collected at baseline\n5. pregnancy or lactation,\n6. Has positive test result(s) for alcohol or drugs of abuse (including methadone, opiates, cocaine, amphetamine\u002Fmethamphetamine, and ecstasy), or substance use disorder including alcohol, stimulants, sedatives, and cannabis exceeding mild severity in the last 6 months,\n7. active suicidal ideation (as measured by Suicide-Risk-Assessment-C-SSRS75 \"Yes\" answers to items 3, 4 or 5 of Suicidal Ideation-Past 1 month section, or any \"Yes\" answer to any of the items of Suicidal Behavior-Past 3 months section), or any suicide attempt in the last 3 months, collected at baseline\n8. MRI contraindications as detected by the MRI Safety Screen, including unwillingness\u002Funable to complete MRI scans\n9. medical history indicative of moderate to severe traumatic brain injury as evidenced by history of \\> 5 minutes of loss of consciousness, or of skull fractures, which in theory could distort LIFU tissue propagation, and\n10. a current diagnosis of a psychotic disorder (e.g. schizophrenia, bipolar disorder), an eating disorder (e.g. anorexia or bulimia nervosa), learning disability, or a personality disorder that is considered by the investigator to interfere with the ability of the subject to adhere to the protocol (e.g., narcissistic personality disorder, borderline personality disorder).\n11. Has a history of moderate or severe substance or alcohol use disorder according to DSM-5-TR\n12. Use of benzodiazepines or anticonvulsants in the 7 days prior ot screening\n13. Medical, psychiatric, or other conditions that restrict the patient's following abilities: to interpret the study information, to give informed consent, to adhere to the rules of the protocol, or to complete the study.\n14. No reliable method of communication (i.e., no access to internet or phone connection)\n15. Prescription of a medication outside of the accepted range, as determined by best clinical practices and current research\n16. Unwilligness or inability to complete any of the major aspects of the study protocol\n17. Non-correctable vision or hearing problems",{"count":120,"type":21},140,[52],"Approximately one third of individuals with Major Depressive Disorder (MDD) are considered treatment-resistant, subject to severe disability and risk of suicide, and exhibit symptoms anchored in abnormalities of Research Domain Criteria (RDoC) Negative Valence Systems behavioral processes. In the present study we plan to use low-intensity focused ultrasound in 120 persons with treatment-resistant MDD to modulate deep white matter tracts connecting the thalamus and different regions of the prefrontal cortex reversibly and non-invasively, with the aim of assigning a causal, mechanistic role to large scale brain circuits in the production of those critical behavioral abnormalities. A successful study will help to attain the precise definition of neuromodulation targets for this clinical population in utter need of help.",[124],"Treatment-Resistant Depression",[124,126],"Low-Intensity Focused Ultrasound","2026-02-27",{"date":129,"type":33},"2026-03-02",{"date":131,"type":33},"2025-09-30",{"date":133,"type":21},"2030-07",{"name":39,"class":40},{"id":136,"slug":137,"hasResults":11,"nctId":138,"briefTitle":139,"officialTitle":139,"acronym":4,"eligibilityCriteria":140,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":141,"targetDuration":4,"studyType":22,"phases":143,"briefSummary":145,"conditions":146,"keywords":152,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":88,"lastUpdatePostDateStruct":159,"startDateStruct":161,"completionDateStruct":163,"leadSponsor":165,"locationsCount":41},"100516407","phase-4-processes-and-circuitry-underlying-threat-sensitivity-as-a-treatment-target-for-co-morbid-anxiety-and-depression-100516407","NCT06004115","Processes and Circuitry Underlying Threat Sensitivity as a Treatment Target for Co-morbid Anxiety and Depression","An individual must meet the following criteria to be considered eligible to participate in the study:\n\nInclusion Criteria:\n\nAll subjects:\n\n* Female or male sex assigned at birth;\n* Age 18-65;\n* Normal or corrected to normal vision\u002Fhearing, as protocol elements may not be valid otherwise;\n* Fluent English speaker, capable of providing written informed consent\n\nMDD and AD-MDD subjects:\n\n* Current major depressive episode assessed by clinician with guidance from the MINI;\n* Minimum score of 55 on PROMIS Depression scale\n\nAD and AD-MDD subjects:\n\n* Current anxiety disorder (generalized anxiety disorder, panic disorder, agoraphobia and social phobia) assessed by clinician with guidance from the MINI;\n* Minimum score of 55 on PROMIS Anxiety Scale\n\nExclusion Criteria:\n\nAll subjects:\n\n* Has uncontrolled, clinically significant neurologic (including seizure disorders): cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the subject to participate or potentially confound the study results;\n* Reported body mass index (BMI) \\> 40;\n* History of moderate or severe traumatic brain injury, as assessed by a TBI questionnaire;\n* History of eating disorder or obsessive-compulsive disorder, schizophrenia, schizo-affective disorder, bipolar disorder or any sign of psychosis;\n* Current post-traumatic stress disorder (PTSD) diagnosis (although history of trauma is allowed);\n* Current use of medications with major effects on brain function or the fMRI hemodynamic response (e.g., methylphenidate, acetazolamide, excessive caffeine intake \\> 1000 mg\u002Fday) following an initial list compiled by LIBR but also assessed on a case-by-case basis. Individuals who are currently on medication (antidepressants such as SSRIs, TCAs, SNRIs, and Bupropion) and who have not undergone dose or medication changes over the past 6 weeks will be allowed to participate;\n* Current benzodiazepine or opiate use;\n* Moderate to severe current substance use disorder, defined as 5 or more symptoms of the criteria for Substance Use Disorder according to DSM 5;\n* Drug or alcohol intoxication (based on positive UTOX or breathalyzer test at screening or study session) or reported alcohol\u002Fdrug withdrawal, last cannabis use must be \\>48 hours prior to study session;\n* Has a risk of suicide according to the Investigator's clinical judgement or per Columbia-Suicide Severity Rating Scale (C-SSRS) or equivalent PhenX instrument, the subject scores \"yes\" on items 4 or 5 in the Suicidal Ideation section with referent to a 30-day period prior to Screening\u002FBaseline or the subject has had one or more suicidal attempts with reference to a 2-year period prior to Screening;\n* MRI contraindications;\n* Is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during this time-period;\n* Any subject judged by the Investigator to be inappropriate for the study.\n\nMDD subjects:\n\n* Current (assessed by clinician with guidance from the MINI) anxiety disorder;\n* Score of \\> 60 on PROMIS Anxiety Scale\n\nAD subjects:\n\n* Current or past recurrent major depressive episodes assessed by clinician with guidance from the MINI;\n* Score of \\> 60 on PROMIS Depression scale",{"count":142,"type":21},165,[144],"PHASE4","This mechanistic study uses an anti anxiety drug and brain imaging to study the threat processing system and associated brain circuits in people with depression, anxiety disorders and comorbid depression and anxiety disorders. In a double blind, placebo controlled crossover design, up to 65 individuals will be recruited who will have a diagnosis of major depressive disorder (MDD) and at least one anxiety disorder (AD) (AD-MDD group), up to 65 participants will have a diagnosis of MDD and no diagnosis of an AD and up to 65 participants will have no diagnosis of MDD and a diagnosis of at least one AD will be enrolled to participate in an two session study to obtain 150 completers (50 per group). All participants will receive a single dose of Lorazepam and placebo (order randomized) taken orally. After the \\~2.5 hr screening session, participants will complete two identical \\~5 hr experimental sessions, each of which include a 30 min eyeblink startle session and a 1.5 hr functional magnetic resonance imaging (MRI) brain scan session. The total time involved in the study is approximately 10.5 hours.\n\nThe main questions the study seeks to answer are:\n\n* are people with comorbid depression and anxiety different than those with depression alone in terms of their eyeblink startle response to threat?\n* are people with comorbid depression and anxiety different than those with depression alone in terms of their brain activation in response to threat?\n* are people with comorbid depression and anxiety different than those with depression alone in terms of their responses to anxiety drugs?",[147,148,104,149,150,151],"Depression, Anxiety","Fear","Anxiety and Fear","Anxiety Disorders","Anxious Depression",[153,154,80,155,156,157,158],"depression","anxiety","threat sensitivity","flight initiation distance","startle reflex","benzodiazepine",{"date":160,"type":33},"2025-10-31",{"date":162,"type":33},"2023-11-08",{"date":164,"type":21},"2027-12-31",{"name":39,"class":40},{"id":167,"slug":168,"hasResults":11,"nctId":169,"briefTitle":170,"officialTitle":171,"acronym":4,"eligibilityCriteria":172,"healthyVolunteers":15,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":173,"targetDuration":4,"studyType":22,"phases":174,"briefSummary":175,"conditions":176,"keywords":178,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":180,"lastUpdatePostDateStruct":181,"startDateStruct":183,"completionDateStruct":185,"leadSponsor":186,"locationsCount":41},"100600627","dose-dependent-effects-of-low-intensity-focused-ultrasound-100600627","NCT07099950","Dose-Dependent Effects of Low-Intensity Focused Ultrasound","Dose-Dependent Functional Connectivity Effects of Low-Intensity Focused Ultrasound Applied to Deep White Matter Tracts in Humans","Inclusion Criteria:\n\n* Age 18 to 65 years.\n* Body mass index 17-38 kg\u002Fm2.\n* Fluent English speaker, capable of providing written informed consent.\n* Overall Anxiety Severity and Impairment Scale \\\u003C8 and Patient Health Questionnaire-9 \\\u003C10\n* A person of childbearing potential must have a negative urine pregnancy test at screening\n* Consent that random observations of pathology are possible (e.g., brain abnormality seen during imaging).\n\nExclusion Criteria:\n\n* Inability to provide informed consent including medical, psychiatric, or other conditions that restrict the patient's following abilities: to interpret the study information, to give informed consent, to adhere to the rules of the protocol, or complete the study.\n* No telephone or easy access to telephone\n* Has active suicidal ideation (as measured by Suicide-Risk-Assessment-C-SSRS \"Yes\" answers to items 3, 4, or 5 Suicidal Ideation-Past 1 month section, or any \"Yes\" answer to any of the items of Suicidal Behavior-Past 3 months section), or any suicide attempt in the last 3 months\n* Has positive test result(s) for alcohol of abuse (including methadone, opiates, cocaine, amphetamine\u002Fmethamphetamine and ecstasy), or substance use disorder including alcohol, stimulants, sedatives, and cannabis exceeding mild severity in the last 6 months\n* Has a lifetime APA Diagnostic and Statistical Manual of Mental Disorders (DSM)-5th edition including major depression, generalized anxiety disorder, specific phobias, panic disorder, post-traumatic stress disorder, schizophrenia spectrum and other psychotic disorders, obsessive-compulsive disorder, or bipolar disorder.\n* Benzodiazepines or anticonvulsants in the 7 days prior to participation.\n* MRI contradictions as detected by the MRI Safety Screen including claustrophobia and unwillingness and inability to complete scans (e.g., unable to lie on one's back for 60 mins.\n* Clinical history of relevant structural pathology of the central nervous system, including Parkinson's disease, multiple sclerosis, and brain malignant neoplasia.\n* History of unstable liver or renal insufficiency; significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, hematological, rheumatological, or metabolic disturbance; or any other condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit or confound the protocol-specified assessments, including uncontrolled diabetes mellitus (ss evidenced by fasting glycemia ≥ 120 mg\u002FdL or hemoglobin A1c ≥ 6.5%) or hypertension (as evidenced by two consecutive readings ≥ 140\u002F90 mmHg) to ensure medical stability throughout this longitudinal study.\n* Moderate-to-severe traumatic brain injury or any other clinical neurocognitive disorder.\n* Clinical history of at least minor neurocognitive disorder of any origin.\n* Prescription of a medication outside of the accepted range, as determined by best clinical practices and current research.\n* Use of any psychotropic medication.\n* Unwillingness or inability to complete any major aspects of the study protocol.\n* Prior neurosurgery.\n* Non-correctable vision or hearing.",{"count":50,"type":21},[52],"Low-intensity focused ultrasound (LIFU) has emerged as a tool to modulate the activity of deep brain structures noninvasively and reversibly, with anatomical precision. Following the results of a pilot study in which the investigators observed target engagement when LIFU was applied to the anterior limb of the internal capsule, the investigators now propose to determine the dose-response relationships of LIFU when applied to deep white matter tracts of the human brain. The investigators hope a successful study will be rapidly translatable into clinical trials seeking to understand mechanistic brain circuit-symptom relationships in major psychiatric disorders.",[177],"Healthy Controls",[126,179],"Functional Connectivity","2025-10-14",{"date":182,"type":33},"2025-10-16",{"date":184,"type":33},"2025-04-22",{"date":37,"type":21},{"name":39,"class":40},{"id":188,"slug":189,"hasResults":11,"nctId":190,"briefTitle":191,"officialTitle":191,"acronym":4,"eligibilityCriteria":192,"healthyVolunteers":11,"sex":193,"minAge":194,"maxAge":195,"enrollmentInfo":196,"targetDuration":4,"studyType":22,"phases":198,"briefSummary":199,"conditions":200,"keywords":204,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":210,"startDateStruct":212,"completionDateStruct":214,"leadSponsor":216,"locationsCount":41},"100541676","interoceptive-mechanisms-of-body-image-disturbance-in-anorexia-nervosa-100541676","NCT06332963","Interoceptive Mechanisms of Body Image Disturbance in Anorexia Nervosa","Inclusion Criteria:\n\n1. Primary diagnosis of anorexia nervosa\n2. Photographic Figure Rating Scale (PFRS) body dissatisfaction score greater than or equal to 1\n3. Eating Disorder Examination Questionnaire (EDE-Q6) Shape Concern Subscale score greater than or equal to 3\n4. Weight restored to body mass index (BMI) greater than or equal to 17.5\n5. No current evidence of orthostatic hypotension or if there is no evidence of additional fall risk as determined by their provider\n6. Clinical status transition from acute to residential status\n7. No new psychiatric medications in the week prior to randomization\n8. Female sex assigned at birth\n9. Ages 13 to 50 years\n10. Independently ambulatory\n11. Ability to lay flat comfortably\n12. English proficiency\n13. Willingness and ability to participate in study procedures\n14. Provision of informed consent (parent consent and minor assent if less than 18 years of age).\n\nExclusion Criteria:\n\n1. Active suicidal ideation with plan and intent\n2. Active cutting or skin lacerating behaviors\n3. Pregnancy as defined by urine screening\n4. Acute intoxication as indicated by urine drug screen or breathalyzer\n5. Orthostatic hypotension as determined by medical provider, evidenced in chart (defined as a drop of ≥ 20 mmHg in systolic blood pressure (BP) or a drop of ≥ 10 mm Hg in diastolic blood pressure (BP) when measured shortly after transitioning from lying down to standing). If evidence of orthostasis is present in chart consultation with provider to determine if status creates additional fall risk. If participant is determined to be at increased fall risk (e.g., dizziness upon standing) they will be excluded.\n6. Seizure reported within the previous 12 months\n7. Co-morbid diagnoses of Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) bipolar disorder, schizophrenia, or other psychosis spectrum disorder\n8. Systolic blood pressure \\> 160 mmHg\n9. Diastolic blood pressure \\>100 mmHg\n10. Resting heart rate \\<50 beats per minute.","FEMALE","13 Years","50 Years",{"count":197,"type":21},102,[52],"The proposed study utilizes a randomized experimental therapeutics design to test a mechanistic framework linking interoceptive processing and disturbed body image, with the purpose of informing the development of future therapies for body image dissatisfaction in anorexia nervosa (AN). A sample of 102 participants will be recruited from the Laureate Eating Disorder Program (LEDP). After being randomized, participants will all receive a one-hour session of acceptance- and mindfulness-based training with a therapist (the introduction session). They will then receive either the interoceptively focused treatment (IFT) or exteroceptively focused treatment (EFT) condition based on randomization. In the IFT condition participants will engage in floatation-REST (Reduced Environmental Stimulation Therapy) while practicing acceptance and mindfulness-based principles. The EFT condition is an exteroceptive intervention in which participants will be asked to view pre-recorded videos of acceptance and mindfulness-based skills to aid in the practice of these skills. Each condition will consist of one introduction session and three experimental sessions. All participants will then return for follow-up measures. Assessed outcomes will include acute changes in body image disturbance (BID) and interoception. Further, longitudinal intervention effects on self-reported eating disorder symptoms, body image dissatisfaction, and interoception; behavioral measures of interoception and body image dissatisfaction; and resting state and interoceptive functioning during functional magnetic resonance imaging (fMRI) will be explored.",[201,202,203],"Anorexia Nervosa","Body Image Disturbance","Interoception",[201,202,205,203,206,207,208],"Perceptual Body Image","Acceptance Based Intervention","Mindfulness Based Intervention","Randomized Clinical Trial","2025-09-25",{"date":211,"type":33},"2025-09-26",{"date":213,"type":33},"2024-04-19",{"date":215,"type":21},"2028-12",{"name":39,"class":40},{"id":218,"slug":219,"hasResults":11,"nctId":220,"briefTitle":221,"officialTitle":222,"acronym":223,"eligibilityCriteria":224,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":225,"targetDuration":4,"studyType":22,"phases":227,"briefSummary":228,"conditions":229,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":232,"lastUpdatePostDateStruct":233,"startDateStruct":235,"completionDateStruct":237,"leadSponsor":239,"locationsCount":41},"100518408","amplification-of-positivity-for-alcohol-use-100518408","NCT06030154","Amplification of Positivity for Alcohol Use","Developing and Evaluating a Positive Valence Treatment for Alcohol Use Disorder With Anxiety or Depression","AMP-A","Inclusion Criteria:\n\n1. Age between 18 and 65 years old.\n2. Meeting diagnostic criteria for alcohol use disorder 42 according to the DSM-5.\n3. Reports that they would like to seek treatment for AUD and that AUD is one of the primary challenges they would like to address in treatment.\n4. Phase 1: Significant depression or anxiety symptoms as indexed by scoring Patient Health Questionnaire (PHQ-9) ≥ 10 and\u002For Overall Anxiety Severity and Impairment Scale (OASIS) ≥ 8. Phase 2: Significant depression or anxiety symptoms as indexed by scoring ≥ 55 on either of the NIH PROMIS ((Patient-Reported Outcomes Measurement Information System) Depression and\u002For Anxiety scales.\n5. Below normative levels of positive affect as indexed by PROMIS Positive Affect \\\u003C50.\n6. Able to provide written informed consent.\n7. Have sufficient proficiency in the English language to understand and complete interviews, questionnaires, and all other study procedures.\n\nExclusion Criteria:\n\n1. Unwillingness or inability to complete any of the major aspects of the study protocol, including self-report or behavioral assessment. However, failing to complete some individual aspects of these assessment sessions will be acceptable (i.e., being unwilling to answer individual items on some questionnaires or being unwilling to complete a behavioral task). In addition, the neuroimaging portion of the protocol will be optional.\n2. Non-correctable vision or hearing problems that interfere with the participant's ability to complete study assessments.\n3. No telephone or easy access to telephone.\n4. Diagnosis of Schizophrenia spectrum, other psychotic disorders, obsessive-compulsive disorder, eating disorders, substance use disorders within the past year other than alcohol use disorder or cannabis use disorder, or bipolar I disorder. Mild binge eating disorder will be considered for inclusion on a case-by-case basis at the discretion of the PI.\n5. Active suicidal ideation with plan and intent to attempt suicide within the next month.\n6. Has a history of unstable liver or renal insufficiency; glaucoma; significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbance; or any other condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments.\n7. A positive test for drugs of abuse, including alcohol (breath test) and substances of dependence that are not physician prescribed (i.e., cocaine, cannabis, opioids, stimulants).at the time of baseline assessments. Participants will be asked to refrain from using alcohol within 24 hours prior to assessment sessions and to refrain from using marijuana within 48 hours of assessment sessions.\n8. Current use of a medication within the 6 weeks prior to enrolling in the study that could potentially affect brain functioning and\u002For the positive valence system (e.g., anxiolytics, antipsychotics, mood stabilizers, opioid antagonists such as naltrexone or other medications specifically targeting alcohol use or cravings). The current use of antidepressants (i.e., SSRIs), benzodiazepines, and psychostimulants will not be excluded as long as the dose has remained consistent for 6 weeks prior to baseline assessment sessions. Individuals who are on stable doses (≥ 6 weeks) of mood stabilizers or antipsychotics may be included if it is determined that they are being prescribed for purposes of treating unipolar depression or anxiety. Inclusion of individuals reporting other types of medications or supplements not listed or considered this far will be at the discretion of the PI according to evidence in the literature of it affecting brain function or brain blood flow.\n9. Taking drugs that affect the fMRI hemodynamic response (e.g., methylphenidate, acetazolamide, and excessive caffeine intake \\> 1000 mg\u002Fday) - Phase 2 only\n10. Concurrent engagement in psychosocial treatments that specifically target alcohol use disorder or mood\u002Fanxiety symptoms and began within 12 weeks of baseline assessments. Individuals concurrently receiving psychosocial treatments for other symptoms, or that are not specifically targeting symptoms (e.g., ongoing support groups) will not be excluded as long as the dose of treatment (i.e., frequency of sessions) has not changed significantly within 6 weeks prior to enrolling in the study.\n11. MRI contraindications (for those in Phase 2 opting into this portion) including: cardiac pacemaker, metal fragments in eyes\u002Fskin\u002Fbody (shrapnel), aortic\u002Faneurysm clips, prosthesis, by-pass surgery\u002Fcoronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates\u002Fpins\u002Fscrews\u002Fwires, or neuro\u002Fbio-stimulators (TENS unit), persons who have ever been a professional metal worker\u002Fwelder, history of eye surgery\u002Feyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60-120 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy - Phase 2 only\n12. Moderate to severe traumatic brain injury (\\>30 min. loss of consciousness or \\>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits, neurological disorders, or severe or unstable medical conditions that might be compromised by participation in the study (to be determined by primary care provider).\n13. Severity of alcohol use disorder requiring more intensive treatment (i.e., intensive outpatient or residential), as determined by licensed clinician determination of American Society of Addiction Medicine (ASAM) Criteria ≥ 0-1 across dimensions, with the exception of a '2' on the emotional dimension.\n14. Given the current study involves development of the positive affect intervention, we will not enroll any special vulnerable populations (pregnant women, fetuses, neonates, prisoners, children).",{"count":226,"type":21},100,[52],"The proposed study consists of two phases. During Phase 1, the investigators will recruit a small sample of participants to complete a psychosocial intervention termed Amplification of Positivity (AMP) for individuals experiencing comorbid depression or anxiety disorders and alcohol use disorder (AMP-A). These participants will be asked to provide both qualitative and quantitative input about the AMP-A intervention. Based on their input and clinician input, the AMP-A manual will be modified for use in Phase 2. The goal is to recruit up to 20 participants in order to ensure there will be at least 8 participants who complete all sessions of AMP-A. Phase 2 is a randomized clinical trial (RCT) protocol in which individuals experiencing comorbid depression or anxiety disorders and alcohol use disorder will be randomized to complete AMP-A or an evidence-based cognitive-behavioral therapy (CBT) intervention. Up to 100 participants will be recruited in order to reach a target of N=60. Assessed outcomes will include participant acceptability and completion rates, participant compliance with the intervention, positive and negative affect, substance use- and depression and anxiety-related symptom severity, functional disability, and neural reactivity to reward and alcohol cues during functional magnetic resonance imaging (fMRI).",[230,231,104],"Alcohol Use Disorder","Anxiety","2025-07-15",{"date":234,"type":33},"2025-07-18",{"date":236,"type":33},"2023-09-25",{"date":238,"type":21},"2026-07",{"name":39,"class":40},{"id":241,"slug":242,"hasResults":11,"nctId":243,"briefTitle":244,"officialTitle":245,"acronym":246,"eligibilityCriteria":247,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":248,"targetDuration":4,"studyType":22,"phases":250,"briefSummary":251,"conditions":252,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":253,"lastUpdatePostDateStruct":254,"startDateStruct":256,"completionDateStruct":258,"leadSponsor":260,"locationsCount":41},"100395237","approach-avoidance-computational-framework-for-predicting-behavioral-therapy-outcome-aac-bet-100395237","NCT04426461","Approach-Avoidance, Computational Framework for Predicting Behavioral Therapy Outcome (AAC-BeT)","An Approach-Avoidance, Computational Framework for Predicting Behavioral Therapy Outcome in Anxiety and Depression (AAC-BeT)","AAC-BeT","Inclusion Criteria:\n\n* score \\>55 on both the PROMIS Anxiety and PROMIS Depression scales\n* score \\>5 on any one item of the SDS\n* able to provide informed consent\n* report of anxiety and depressive symptoms as areas of clinical concern\n* sufficient English proficiency to complete procedures.\n\nExclusion Criteria:\n\n* significant or unstable physical or mental health conditions (e.g., immediate suicidal intent) requiring medical attention\n* history of bipolar, psychotic, cognitive, obsessive compulsive disorder, posttraumatic stress disorder (PTSD)\n* history of moderate to severe substance use disorder over the past year\n* diagnosis of neurologic disorders\n* MRI contra-indications (e.g., metal in body)\n* uncorrected vision\u002Fhearing problems\n* current, regular benzodiazepine use",{"count":249,"type":21},220,[52],"Depression and anxiety disorders rank in the top ten causes of years lived with disability. Less than 50% of patients experiencing long-lasting improvements to current gold-standard treatments. Two gold-standard behavioral interventions include behavioral activation, focused on enhancing approach behavior towards meaningful activities, and exposure-based therapy, focused on decreasing avoidance and challenging negative expectations. While these interventions have divergent treatment targets, there is little knowledge to inform which strategies should be used in the frequent case of comorbid anxiety and depression. Approach-avoidance decision-making paradigms focus on assessing responses when faced with potential rewards and threats, tapping into processes important for both anxiety and depression as well as behavioral activation and exposure-based therapy.\n\nFor this study, investigators will recruit individuals reporting both anxiety and depression symptoms and randomize them to one of three different interventions: (1) behavioral activation, (2) exposure-based therapy, and a non-specific therapy approach (3) supportive therapy. Participants will complete clinical, self-report, behavioral, and functional magnetic resonance imaging (fMRI) assessments before and after therapy. Investigators will use a computational approach to model factors that may influence one's behavior during approach-avoidance decision-making, including drives to avoid threat versus approach reward and confidence versus uncertainty in one's decisions.\n\nThis project will accomplish the following aims (1) Determine how changes in brain and behavior responses during approach-avoidance conflict relate to changes in mental health symptoms with the different therapy approaches, (2) Determine the degree to which baseline brain and behavior responses during approach-avoidance conflict predict response to the different therapy approaches, above and beyond the influence of demographics and baseline symptom severity. In addition, by including peripheral blood draws and measures of grace matter volume, the project will also accomplish the following aims: (1) Determine whether kynrenine metabolites measures peripherally may be beneficial as a biomarker of treatment response and (2) determine whether there is an association between change in kynurenine metabolites and changes in gray matter volume with treatment.\n\nResults will enhance understanding of how different psychotherapy approaches (behavioral activation, exposure-based therapy) may impact brain responses and decisions when faces with potential reward versus threat and approach versus avoidance drives. In addition, results will have important implications concerning the potential for a more personalized approach to psychotherapy, enhancing knowledge of which types of therapy strategies may be most beneficial for which individuals.",[231,104],"2025-06-12",{"date":255,"type":33},"2025-06-13",{"date":257,"type":33},"2020-09-11",{"date":259,"type":21},"2025-06-30",{"name":39,"class":40},{"id":262,"slug":263,"hasResults":11,"nctId":264,"briefTitle":265,"officialTitle":265,"acronym":4,"eligibilityCriteria":266,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":267,"enrollmentInfo":268,"targetDuration":4,"studyType":22,"phases":270,"briefSummary":271,"conditions":272,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":274,"lastUpdatePostDateStruct":275,"startDateStruct":277,"completionDateStruct":279,"leadSponsor":281,"locationsCount":41},"100522908","phase-1-effects-of-acute-exercise-and-ibuprofen-on-symptoms-immunity-and-neural-circuits-in-bipolar-depression-100522908","NCT06088732","Effects of Acute Exercise and Ibuprofen on Symptoms, Immunity, and Neural Circuits in Bipolar Depression","Inclusion Criteria:\n\n1. Provision of signed and dated informed consent form\n2. Has an established residence and phone\n3. Agrees to and is eligible for behavioral testing, magnetic resonance imaging, and blood draws.\n4. Stated willingness to comply with all study procedures and lifestyle considerations (see Section 5.3, Lifestyle Considerations) and availability for the duration of the study\n5. Males and females; Age 18-55 years\n6. DSM-V diagnosis of bipolar disorder\n7. Has a current major depressive episode\n8. Depression at enrollment of sufficient severity to score \\> 11 on the QIDS\n9. Be stably medicated for at least 4 weeks (a non-medicated subject may be included in the study if judged to be appropriate in the medical\u002Fpsychiatric opinion of the investigator)\n10. BMI between 18.5 and 35\n\nExclusion Criteria:\n\n1. Diagnosis of any other major psychiatric disorder such as schizoaffective disorder, schizophrenia, or current psychotic depression\n2. A history of bipolar disorder with rapid cycling\n3. Concurrent manic symptoms of sufficient severity to pose a substantial risk of the development of a manic episode (\\>19 on the YMRS)\n4. Current drug or alcohol or substance use disorder moderate or severe, except nicotine (within 6 months for severe use disorder; 2 months for moderate use disorder)\n5. Volunteers currently receiving more than 4 mood-relevant psychotropic medications in a daily regimen (since this may signify a more brittle or complex clinical state)\n6. Taking any of the following medications: medications with significant interactions with ibuprofen; immune-modulating medications (e.g. oral steroids); regular use of NSAIDs (\\> 3 times per week)\n7. Current or prior cardiac disease, cardiac arrhythmia (e.g. supraventricular tachycardia, atrial fibrillation, ventricular fibrillation), or history of cardiac ablation therapy\n8. Unstable medical condition, including significant respiratory disease (e.g., asthma, reactive airway disease (i.e., exercise induced asthma), or chronic obstructive pulmonary disease (COPD)), liver disease, hypothyroidism (i.e., condition not adequately stabilized for 3 months), or other conditions likely to require hospitalization or with a life expectancy of \\\u003C 6 months (e.g., cancer).\n9. History of claustrophobia that would prevent participation in imaging scans\n10. Actively suicidal, as defined by expressive ideation with a plan and intent for suicide or developing suicidal ideation that requires immediate medical or treatment intervention or a suicide attempt within the previous six months\n11. Participants who endorse a history of moderate to severe traumatic brain injury (\\>30 min. loss of consciousness or \\>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits\n12. Inadequate understanding of English\n13. Currently pregnant or breast-feeding; fecund women not using adequate contraceptive methods; plan to become pregnant within 12 months\n14. Metal in the body (e.g. history of working as a sheet metal worker) or pacemaker which is a contra-indication to magnetic resonance imaging\n15. Has epilepsy, a neuromuscular disorder, or tardive dyskinesia\n16. Has a chronic infectious illness\n17. Requires immediate hospitalization for psychiatric disorder\n18. Requires medications for a general medical condition that contraindicate any study medication\n19. Receiving or have received during the index episode vagus nerve stimulation, electroconvulsive therapy, transcranial magnetic stimulation, or other somatic treatments\n20. Allergy to, or other medical contraindication to ibuprofen (e.g. stomach ulcers)\n21. Symptoms of myalgic encephalomyelitis\u002Fchronic fatigue syndrome or \"long-COVID\".\n22. Current use of medications or dietary supplements for weight or appetite control, whether prescribed or not\n23. Ulcerative colitis, Crohn's disease or other autoimmune disorder (except treated hypothyroidism)\n24. Activity restrictions that limit the subject's ability to engage in intense physical activity\n25. Use of beta-blockers, calcium channel inhibitors, or other heart-modulating medications (e.g., amiodarone)\n26. Clinically significant abnormality on EKG\n27. Hypertension, hepatitis, renal dysfunction, and\u002For anemia of sufficient severity to pose a risk to the participant\n28. Moderate or heavy smoker based on Fagerstrom\n29. Resting heart rate \\>100 beats per minute, systolic blood pressure \\> 160 mmHg, diastolic blood pressure \\> 100 mmHg\n30. Clinically significant screening laboratory abnormalities not covered above\n31. Any reason not listed herein that would make participation in the study hazardous","55 Years",{"count":269,"type":21},20,[24,25],"This is a 2x2, within-subjects, cross-over trial to test the anti-depressant effects of acute exercise in 20 participants with bipolar depression. Participants will complete four experimental sessions, two with an exercise challenge and two with a resting control condition in a counterbalanced order. Participants will receive either 800mg of ibuprofen or placebo before exercise or rest in order to test whether blocking the inflammatory response to exercise interferes with the neural and psychological effects of exercise.",[273],"Bipolar Depression","2025-05-20",{"date":276,"type":33},"2025-05-23",{"date":278,"type":33},"2024-03-12",{"date":280,"type":21},"2026-12-31",{"name":39,"class":40},{"id":283,"slug":284,"hasResults":11,"nctId":285,"briefTitle":286,"officialTitle":287,"acronym":4,"eligibilityCriteria":288,"healthyVolunteers":15,"sex":193,"minAge":289,"maxAge":290,"enrollmentInfo":291,"targetDuration":4,"studyType":22,"phases":293,"briefSummary":294,"conditions":295,"keywords":296,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":297,"lastUpdatePostDateStruct":298,"startDateStruct":300,"completionDateStruct":302,"leadSponsor":304,"locationsCount":41},"100447864","gastrointestinal-interoception-in-anorexia-nervosa-100447864","NCT05111977","Gastrointestinal Interoception in Anorexia Nervosa","A Neurocomputational Assay of Gastrointestinal Interoception in Anorexia Nervosa","Inclusion Criteria:\n\nHC Inclusion criteria:\n\ni. Body mass index ≥ 18.5. ii. Females, ages 15 to 40 years iii. Women of childbearing age: a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study.\n\niv. Independently ambulatory v. Possession of a smartphone with data plan vi. English proficiency vii. Willingness and ability to participate in study procedures viii. Provision of signed and dated informed consent form\n\nAN Inclusion criteria:\n\ni. Primary clinical diagnosis of anorexia nervosa as defined by Laureate Eating Disorders Program ii. Body mass index ≥ 18.5. iii. Transitioned from acute clinical status rating to residential clinical status or partial\u002Fintensive outpatient clinical status rating iv. No new medication prescription in the week prior to study randomization, Must be on a stable dose of medication for at least 1 week.\n\nv. Females, ages 15 to 40 years vi. Women of childbearing age: a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study.\n\nvii. Independently ambulatory viii. Possession of a smartphone with data plan ix. English proficiency x. Willingness and ability to participate in study procedures xi. Provision of signed and dated informed consent form\n\nExclusion Criteria:\n\nHC Exclusion criteria:\n\ni. Current diagnosis of a psychiatric disorder per the MINI International Diagnostic Interview\n\nii. Taking any psychotropic medication\n\niii. Active suicidal ideation with intent or plan\n\niv. Active cutting or skin lacerating behaviors\n\nv. Active purging behaviors (specifically, self-induced vomiting), and\u002For a history of severe self-induced vomiting\n\nvi. Pregnancy as defined by a urine screen during screening, and confirmed during each stimulation visit, and must not be lactating\n\nvii. History of significant gastrointestinal disorder, including any form of inflammatory bowel disease or gastrointestinal malignancy (celiac disease is accepted if the subject has been treated and is in remission)\n\nviii. History of complicated\u002Fobstructive diverticular disease\n\nix. Clinical evidence of significant gastroparesis\n\nx. Diagnosis of mega-rectum or colon, congenital anorectal malformation, or clinically significant rectocele or rectal prolapse\n\nxi. History of intestinal or colonic obstruction, or suspected intestinal obstruction\n\nxii. History of intestinal resection (with an exception for appendectomy, cholecystectomy and inguinal hernia repair), history of bariatric surgery or evidence of any structural abnormality of the gastrointestinal tract that might affect transit\n\nxiii. History of Zenker's diverticulum, dysphagia, Barrett's esophagus, esophageal stricture or achalasia, transesophageal fistula, or eosinophilic esophagitis.\n\nxiv. Clinical evidence (as judged by the investigator) of respiratory, cardiovascular, renal, hepatic, biliary, endocrine, or neurologic disease\n\nxv. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs): chronic use is defined as taking full dose NSAIDs more than three times a week for at least six months. Subjects on cardiac doses of aspirin may be enrolled in the study\n\nxvi. Cardiac pacemaker, implantable cardioverter defibrillator, implantable infusion device, or gastric electrical stimulator\n\nxxv. Orthostatic hypotension (defined as a drop of ≥ 20 mm Hg in systolic BP or a drop of ≥ 10 mm Hg in diastolic BP when measured shortly after transitioning from lying down to standing)\n\nxxvi. Any other condition which in the opinion of the investigator may adversely affect the safety of the subject or would limit the subject's ability to complete the study\n\nxxvii. No smartphone\u002Fcomputer or limited access to a smartphone\u002Fcomputer\n\nxxviii. Regular use of any of the following medications or procedures: Medications that may substantially affect intestinal motility, prokinetics at high doses (metoclopramide, erythromycin, senna, prucalopride), anti-Parkinsonian medications, opiates, opioids, calcium-channel blockers, enemas\n\nxxix. History of a GI bleed within the last 3 months\n\nxxx. Pelvic floor dysfunction\u002Fdefecatory disorder, based on subject history\n\nxxxi. Planning to undergo MRI during study time frame\n\nxxxii. Any known allergy to soybean or beeswax or Calcium Carbonate\n\nxxxiii. Bradycardia less than 40 beats per minute\n\nxxxiv. Pain Disorder\n\nAN Exclusion criteria:\n\ni. Active suicidal ideation with intent or plan\n\nii. Active cutting or skin lacerating behaviors\n\niii. Active purging behviors (specifically, self-induced vomiting), and\u002For a history of severe self-induced vomiting\n\niv. Pregnancy as defined by a urine screen during screening, and confirmed during each stimulation visit, and must not be lactating\n\nv. History of significant gastrointestinal disorder, including any form of inflammatory bowel disease or gastrointestinal malignancy (celiac disease is accepted if the subject has been treated and is in remission)\n\nvi. History of complicated\u002Fobstructive diverticular disease\n\nvii. Clinical evidence of significant gastroparesis\n\nviii. Diagnosis of mega-rectum or colon, congenital anorectal malformation, or clinically significant rectocele or rectal prolapse\n\nix. History of intestinal or colonic obstruction, or suspected intestinal obstruction\n\nx. History of intestinal resection (with an exception for appendectomy, cholecystectomy and inguinal hernia repair), history of bariatric surgery or evidence of any structural abnormality of the gastrointestinal tract that might affect transit\n\nxi. History of Zenker's diverticulum, dysphagia, Barrett's esophagus, esophageal stricture or achalasia, transesophageal fistula, or eosinophilic esophagitis.\n\nxii. Clinical evidence (as judged by the investigator) of respiratory, cardiovascular, renal, hepatic, biliary, endocrine, or neurologic disease\n\nxiii. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs): chronic use is defined as taking full dose NSAIDs more than three times a week for at least six months. Subjects on cardiac doses of aspirin may be enrolled in the study\n\nxiv. Cardiac pacemaker, implantable cardioverter defibrillator, implantable infusion device, or gastric electrical stimulator\n\nxv. Orthostatic hypotension (defined as a drop of ≥ 20 mm Hg in systolic BP or a drop of ≥ 10 mm Hg in diastolic BP when measured shortly after transitioning from lying down to standing)\n\nxvi. Any other condition which in the opinion of the investigator may adversely affect the safety of the subject or would limit the subject's ability to complete the study\n\nxvii. No smartphone\u002Fcomputer or limited access to a smartphone\u002Fcomputer\n\nxviii. Regular use of any of the following medications or procedures: Medications that may substantially affect intestinal motility, prokinetics at high doses (metoclopramide, erythromycin, senna, prucalopride), anti-Parkinsonian medications, opiates, opioids, calcium-channel blockers, enemas\n\nxix. History of GI bleed within the last 3 months\n\nxx. Pelvic floor dysfunction\u002Fdefecatory disorder, based on subject history\n\nxxi. Planning to undergo MRI during study time frame\n\nxxii. Any known allergy to soybean or beeswax, or Calcium Carbonate\n\nxxiii. Bradycardia less than 40 beats per minute\n\nxxiv. Pain Disorder","15 Years","40 Years",{"count":292,"type":21},150,[52],"Anorexia nervosa (AN) has among the highest mortality rate of any psychiatric illness, yet we have a poor understanding of the biological causes of this disorder. In this study, we use a novel mechanosensory intervention to examine the basic question of whether individuals with AN have abnormal \"gut sensations\" and whether such indicators are associated with adverse consequences from the disorder.",[201],[203],"2024-05-09",{"date":299,"type":33},"2024-05-10",{"date":301,"type":33},"2021-12-01",{"date":303,"type":21},"2026-07-31",{"name":39,"class":40},""]