[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"mci-with-increased-risk-for-alzheimer-disease\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:mci-with-increased-risk-for-alzheimer-disease":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,41],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":40},"100640268","ultrasonic-debris-clearance-to-promote-brain-resilience-100640268",false,"NCT07573982","Ultrasonic Debris Clearance to Promote Brain Resilience","Safety and Feasibility Trial of Ultrasonic Debris Clearance to Promote Brain Resilience","Inclusion Criteria:\n\n1.1. Physician-reported amyloid positivity diagnosed by amyloid positron emission tomography (PET) OR historic CSF positivity of Abeta42, total tau, or phosphorylated tau OR positivity of plasma pTau-217.\n\n1.2. Age ≥ 18 years. No gender\u002Fsex, racial, or ethnic preference. Subjects greater than 60 years of age will be assumed to be non-pregnant based on age and expected post-menopausal status. Female subjects under the age of 60 will complete a two-step assessment of pregnancy status (a self-reported assessment of menopause that proceeds to a urine human chorionic gonadotropin (hCG) test to confirm non-pregnancy, if the participant is not post-menopausal).\n\n1.3. CDR Scale score less than or equal to 1.0, consistent with mild, very mild, or no dementia.\n\n1.4. Ability and willingness to comply with the study procedures (six sessions sitting in a procedure chair for up to one hour for the procedure, with an ultrasound device placed on their scalp; additional time for the MRI assessment, blood draws, and cognitive assessments).\n\n1.5. Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n2.1. Dementia of moderate or higher severity (CDR \\> 1.0) 2.2. Intracranial tumors, acute or chronic hemorrhage (beyond petechiae\u002Fmicrohemmorhage), or other current or historic central nervous system specific pathology. Baseline MRI studies will be screened by the protocol director to ensure no exclusionary intracranial pathology is present.\n\n2.3. Any other comorbidity that would prevent adequate interpretation of the study results per the treatment team (e.g. congenital brain malformations without clinical importance) 2.4. Ultrasound attenuators along the ultrasound beam path (metal, air, or bulky calcification) including thick hair or related adornments that cannot be undone for the study (e.g. turbans, dreadlocks, hairweaves\u002Fwigs) that would prevent adequate ultrasound gel coupling of the device to the scalp or could trap air in the ultrasound beam path.\n\n2.5. Contraindications to MRI (unknown device, claustrophobia) or metallic hardware in the head that prevent adequate MRI visualization of the brain 2.6. Allergy or similar intolerance to the materials used for ultrasound device coupling (ultrasound gel, silicone) 2.7. Receipt of anti-amyloid monoclonal antibody therapy within 6 months prior to screening 2.8. Moderate or greater depressive symptoms at screening, defined as a Patient Health Questionnaire-9 (PHQ-9) total score \\>= 10.\n\n2.9. Clinically significant suicidal ideation or behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) 2.10. Clinically significant hematologic abnormalities, defined as hematocrit \\\u003C 35% for male or \\\u003C 32% for female, absolute neutrophil cell count \\\u003C 1500\u002FuL, absolute lymphocyte count \\\u003C 900\u002FuL, or platelet count \\\u003C 120,000\u002FuL 2.11. Clinically significant hepatic, renal, respiratory, cardiovascular, or metabolic disease that increases risk or interferes with interpretation, defined as ALT\u002FAST\u002FALP \\> 1.5 ULN, or eGFR \\\u003C 50 mL\u002Fmin\u002F1.73m2, or recent MI\u002Funstable angina\u002FHF\u002Fcardiomyopathy within 6 months, 2.12. Significant bradycardia(\\\u003C50\u002Fmin) or tachycardia (\\>100\u002Fmin) 2.13. Poorly controlled BP 2.14. Uncontrolled diabetes, defined as HbA1c \\> 7.5 2.15. Active clinically significant infection or other systemic illness affecting the CNS","ALL","18 Years",{"count":19,"type":20},15,"ESTIMATED","INTERVENTIONAL",[23],"NA","This pilot study will evaluate the safety, tolerability, and feasibility of Ultrasonic Debris Clearance (UDC), a noninvasive low-intensity focused ultrasound intervention, in amyloid-positive adults who are asymptomatic but at risk for Alzheimer's disease, or who have mild cognitive impairment or mild dementia. The study is designed to test whether repeated UDC sessions can be delivered safely and feasibly in this population, while also exploring efficacy via biomarkers and clinical measures.",[26,27],"Alzheimer s Disease","MCI With Increased Risk for Alzheimer Disease","NOT_YET_RECRUITING","2026-05-01",{"date":31,"type":32},"2026-05-07","ACTUAL",{"date":34,"type":20},"2026-07",{"date":36,"type":20},"2027-07",{"name":38,"class":39},"Stanford University","OTHER",1,{"id":42,"slug":43,"hasResults":11,"nctId":44,"briefTitle":45,"officialTitle":46,"acronym":47,"eligibilityCriteria":48,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":50,"enrollmentInfo":51,"targetDuration":4,"studyType":21,"phases":53,"briefSummary":55,"conditions":56,"keywords":60,"overallStatus":68,"whyStopped":4,"lastUpdateSubmitDate":69,"lastUpdatePostDateStruct":70,"startDateStruct":72,"completionDateStruct":74,"leadSponsor":76,"locationsCount":40},"100565215","phase-2-repurposing-siponimod-for-alzheimers-disease-100565215","NCT06639282","Repurposing Siponimod for Alzheimer's Disease","SIPO1-AD: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients With Mild Alzheimer's Disease","SIPO1-AD","Inclusion Criteria:\n\n1. Male or female at least 50 years of age, but less than 85 (84 at time of screening)\n2. Females must be of non-childbearing potential or have negative pregnancy test at time of screening. Women of non-childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy or bilateral salpingectomy) or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for \\>12 months prior to the planned date of enrollment.\n3. Must have a diagnosis of mild Alzheimer's Dementia determined by medical record review.\n4. Vision and hearing must be sufficient to comply with study procedures.\n5. Be able to take oral medications.\n6. Must be able to attend all study visits indicated in the schedule of visits.\n7. Must have a collateral informant\u002Fstudy partner who has significant direct contact with the patient at least 10 hours per week and who is willing to accompany the patient to specified clinic visits, supervise administration of all study medication, and be available for telephone visits\u002Finterviews.\n8. Documented Mini Mental State Exam (MMSE) score between 20-26 at Screening Visit Day 1.\n9. CT or MRI scan of the brain within 12 months of Screening Visit Day 1 showing no evidence of significant focal lesions or other pathology which could contribute to dementia. If neither a CT or a MRI scan is available from the past 12 months, a scan fulfilling the requirements must be obtained before randomization.\n10. Hachinski ischemic score must be \\\u003C 4.\n11. Geriatric depression scale must be \\\u003C 10.\n12. Prior to dosing all randomized study subjects must show proof they have received immunization to varicella (VZV IgG).\n13. Each patient must be assessed for capacity to consent by the principal or sub-investigators in order to provide informed consent. If the patient is deemed unable to provide informed consent, they must have a legally authorized representative (LAR), and the LAR must review and sign the informed consent form. If the patient does not have a LAR, the patient must appear able to provide informed consent and must review and sign the informed consent form. If the patient is deemed unable to provide informed consent and does not have a LAR, they cannot participate in the study. In addition, the patient's study partner\u002Finformant (as defined in the study inclusion criteria) must sign the informed consent form. If the LAR and the patient's study partner\u002Finformant are the same individual, he\u002Fshe should sign under both.\n14. No active suicidality identified on Columbia-Suicide Severity Rating Scale (C-SSRS).\n15. Patients with stable prostate cancer may be included at the discretion of the Medical Monitor.\n16. Patients who are on monoclonal antibody medication for the treatment of Alzheimer's (ex. lecanemab, donanemab) for \\> 6 months or have discontinued monoclonal antibody medication for the treatment of Alzheimer's for \\> 6 months may be included if all other criteria has been met.\n\nExclusion Criteria:\n\n1. Taking one of the following medications: Medications for treatment of cancer or other drugs that weaken the immune system (ex. Natalizumab and Rituximab), Amiodarone, Bishydroxycoumarin, Chloramphenicol, Cimetidine, Fluconazole, Fluvastatin, Miconazole, Phenylbutazone, Sulphinpyrazone, Sulphadiazine, Sulphamethizole, Sulfamethoxazole, Sulphaphenazole, Trimethoprim, and Zafirlukast.\n2. Current active infection in participants including, but not limited to, herpes zoster, herpes infection, bronchitis, sinusitis, upper respiratory infection and fungal skin infection. Siponimod may increase the risk in participants with active infections.\n3. If participant received mRNA COVID-19 vaccination, must have received last dose at least 3 months prior to first dose of study drug\u002Fplacebo.\n4. Current evidence or history within the last 3 years of a neurological or psychiatric illness that could contribute to dementia, including (but not limited to) epilepsy, focal brain lesion, Parkinson's disease, seizure disorder, or head injury with loss of consciousness.\n5. Meets DSM IV criteria for any major psychiatric disorder including psychosis, major depression and bipolar disorder.\n6. Known history of or self-reported active alcohol and\u002F or substance abuse within the past three years.\n7. Isolated living circumstances which would prohibit a study partner from providing sufficient and credible information about the participant.\n8. Poorly controlled hypertension\n9. Known Atrioventricular heart block, known heart block type I-III.\n10. History of myocardial infarction or signs or symptoms of unstable coronary artery disease within the last year (including revascularization procedure\u002Fangioplasty).\n11. Severe pulmonary disease (including chronic obstructive pulmonary disease) requiring more than 2 hospitalizations within the past year.\n12. Untreated obstructive sleep apnea.\n13. Any thyroid disease (unless euthyroid on treatment for at least 6 months prior to screening).\n14. Active neoplastic disease (except for skin tumors other than melanoma) within five years.\n15. Absolute lymphocytopenia of \\\u003C1,000\u002Fmm3, or a history of lymphocytopenia within the past two years.\n16. Absolute neutropenia of \\\u003C1,000\u002Fmm3, or a history of neutropenia within the past two years.\n17. History of\u002F or current thromboembolism (including deep venous thrombosis).\n18. Any clinically significant hepatic or renal disease (including presence of Hepatitis B or C surface antigen or an elevated transaminase levels of greater than 2x the upper limit of normal (ULN) or creatinine greater than 1.5 x upper limit of normal (ULN)).\n19. Clinically significant hematologic or coagulation disorder including any unexplained anemia, or a platelet count less than 100,000\u002FµL at screening.\n20. Use of any investigational drug within 30 days or within five half-lives of the investigational agent, whichever is longer.\n21. Unwilling or unable to undergo CT or MRI imaging.\n22. In the opinion of the investigator, participation would not be in the best interest of the subject.\n23. Subjects with CYP2C9\\*3\u002F\\*3 genotyping","50 Years","85 Years",{"count":52,"type":20},105,[54],"PHASE2","Collaboration with multiple sclerosis (MS) specialty colleagues led us to formulate the central hypothesis that Siponimod could lower the rate of brain atrophy in Alzheimer's disease (AD) subjects. To test our central hypothesis, we will carry out an 18-month Phase II, double-blind, randomized, twoarmed, placebo controlled, proof-of-concept clinical study in early AD subjects (i.e. mild AD) who will be receiving an escalating dose of Siponimod or placebo in the ratio 2:1 for 12 months, followed by a 6-month washout period. The primary outcome measures are safety and tolerability of Siponimod in mild AD subjects. The secondary outcome measures are the rates of brain atrophy derived from volumetric MRI (vMRI) as a proxy for neurodegeneration conducted at baseline, 6, 12, and 18 months. The tertiary outcome measures are the changes in cognition and the levels of AD-associated (e.g., Aβ and tau) and inflammatory biomarkers in CSF after Siponimod exposure. In an exploratory effort, we will also measure plasma inflammatory markers during the entire duration of the study to investigate whether one or more of these markers can be used as dynamic surrogate markers of treatment response. Using our unique experience with the repurposing of immunomodulatory drugs for AD (and NCT #04032626), in the present project we are using elements of clinical trial design that we believe were successful and made some adjustments to fit the pharmacologic and toxic properties of Siponimod.",[57,58,27,59],"Alzheimer Disease","Mild Alzheimer Disease","Cognitive Impairment, Mild",[61,62,63,64,65,66,67],"Alzheimer's disease","Siponimod","Cognitive Impairment","Cognition","Brain Imaging","Biomarkers","Immunomodulation","RECRUITING","2026-03-02",{"date":71,"type":32},"2026-03-04",{"date":73,"type":32},"2025-08-26",{"date":75,"type":20},"2029-10",{"name":77,"class":39},"St. Joseph's Hospital and Medical Center, Phoenix"]