[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657637":3},{"organization":4,"outcomesModule":7,"designInfo":52,"detailedDescription":65,"studyPopulation":51,"armGroups":66,"interventions":77,"overallOfficials":87,"centralContacts":95,"locations":105,"responsibleParty":128,"collaborators":131,"id":136,"slug":137,"hasResults":138,"nctId":139,"briefTitle":140,"officialTitle":141,"acronym":142,"eligibilityCriteria":143,"healthyVolunteers":138,"sex":144,"minAge":145,"maxAge":146,"enrollmentInfo":147,"targetDuration":51,"studyType":150,"phases":151,"briefSummary":153,"conditions":154,"keywords":158,"overallStatus":107,"whyStopped":51,"lastUpdateSubmitDate":161,"lastUpdatePostDateStruct":162,"startDateStruct":165,"completionDateStruct":167,"leadSponsor":169,"locationsCount":170},{"fullName":5,"class":6},"University Hospital, Akershus","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":51},[9],{"measure":10,"description":11,"timeFrame":12},"Mean between-group differences in plasma p-Tau217","Mean overall between-group differences in plasma p-Tau217 (as the core blood-based biomarker of AD) from baseline to week 48.","Baseline and Week 48.",[14,18,22,26,29,33,36,39,43,47],{"measure":15,"description":16,"timeFrame":17},"Mean difference from baseline in GFAP in patients receiving Urolithin A versus placebo","Blood samples will be assessed for changes from baseline in plasma GFAP in patients receiving Urolithin A versus placebo.","Baseline, and then at Week 24 and Week 48.",{"measure":19,"description":20,"timeFrame":21},"Mean difference in mitophagy\u002Fautophagy biomarkers in patients receiving urolithin A versus placebo","Mean difference in the mean plasma levels of PINK1, ULK1, BNIP3L, TFEB, LC3, p62, cathepsins, and NAD+ as markers of mitochondrial and cellular resilience from baseline.","Baseline, and then week 24 and week 48.",{"measure":23,"description":24,"timeFrame":25},"Change from baseline in blood lipofuscin-like pigment relative fluorescence intensity","Lipofuscin-like pigments (LFPs), reflecting lipid peroxidation end-products, will be measured in blood-derived samples (erythrocytes and plasma) using fluorescence spectroscopy. The outcome will be reported as relative fluorescence intensity, calculated as the ratio of fluorescence intensity at predefined fluorescence maxima to the reference fluorescence intensity. Higher values indicate higher accumulation of lipophilic oxidation products \u002F greater oxidative damage.","Baseline, and then at week 24 and week 48.",{"measure":27,"description":28,"timeFrame":21},"Change from baseline in cellular reactive oxygen species fluorescence intensity in erythrocytes and plasma.","Determination of mean fluorescence intensity of cellular reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) will be assessed by flow cytometry using dihydroethidium (DHE). The outcome will be reported as mean fluorescence intensity. Higher values indicate higher cellular ROS levels",{"measure":30,"description":31,"timeFrame":32},"Change from baseline in mitochondrial reactive oxygen species fluorescence intensity in PBMCs","Mitochondrial reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) will be assessed by flow cytometry using MitoSOX. The outcome will be reported as mean fluorescence intensity. Higher values indicate higher mitochondrial ROS levels.","Baseline, and then Week 24 and Week 48.",{"measure":34,"description":35,"timeFrame":17},"Multi-omic profiling for systemic variation from baseline in cytokines and markers of inflammation between those receiving UA versus placebo.","Participant PBMC samples will be assessed for mean differences in multi-omic analysis panels, including RNA-seq, proteomics and metabolomics, and targeted identification of inflammation-based cytokines such as IL-1β, IL-6, CRP, TNF-α, as appropriate.",{"measure":37,"description":38,"timeFrame":17},"Change from baseline in the modified Preclinical Alzheimer's Cognitive Composite (mPACC) score","Cognitive change will be assessed using the modified Preclinical Alzheimer's Cognitive Composite (mPACC), calculated as an aggregated composite z-score from these tests: Memory Binding Immediate - Total paired recall (immediate associative episodic memory performance, scored from 0-32), Memory Binding Delayed - Total delayed free recall (delayed episodic memory performance, scored 0-32), Digit Symbol coding (processing speed and attention performance, scored 0-133), and Semantic verbal fluency (semantic fluency performance; no fixed maximum raw score; 1 minute per category for animal and vegetable categories). Higher individual scores indicate better memory performance in all batteries, and therefore a higher overall score indicates better memory performance. Unit of Measure: Composite z-score.",{"measure":40,"description":41,"timeFrame":42},"Number of participants with adverse events and serious adverse events","Safety and tolerability will be assessed by recording adverse events (AEs) and serious adverse events (SAEs) throughout the study period using CTCAE criteria. An AE will be defined as any untoward medical occurrence, whether or not considered related to the study supplement. A SAE will be defined as an event that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, results in persistent or significant disability\u002Fincapacity, or is otherwise considered medically important by the investigator. Participants will undergo a safety and tolerability interview during scheduled visits. All reported AEs and SAEs will be assessed by the investigator for seriousness, severity, and relationship to the study supplement. Unit of measure: Number of participants displaying symptoms.","From baseline through Week 48, including scheduled safety\u002Ftolerability assessments at Weeks 12, 24, 36, and 48.",{"measure":44,"description":45,"timeFrame":46},"Study supplement adherence","Adherence to the study supplement intake schedule will be assessed using a mobile app for daily monitoring and structured compliance checks during scheduled visits. Adherence will be reported as the percentage of planned daily doses taken during the study period. Unit of Measure: Percentage of planned doses taken.","Throughout the study (mobile app), and at participant control visits at Weeks 12, 24, 36, and 48.",{"measure":48,"description":49,"timeFrame":50},"To identify UA exposure in cerebrospinal fluid (CSF)","In a voluntary sub-cohort, CSF samples will be collected at baseline and Week 4 to assess UA levels \u002F CNS exposure.","Baseline and week 4.",null,{"allocation":53,"interventionModel":54,"interventionModelDescription":55,"primaryPurpose":56,"observationalModel":51,"timePerspective":51,"maskingInfo":57},"RANDOMIZED","PARALLEL","A double-blind, single centre, randomised, placebo-controlled trial","SUPPORTIVE_CARE",{"masking":58,"maskingDescription":59,"whoMasked":60},"QUADRUPLE","All participants, caregivers, clinical investigators, care providers, and outcome assessors will remain blinded to treatment allocation. Emergency unblinding will be available through an independent unblinded safety\u002Frandomisation contact if required for participant safety.",[61,62,63,64],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR","Alzheimer's disease (AD) is one of the leading causes of dementia and, eventually, death in the elderly. Although AD has been known for generations, its causes have proven to be quite elusive, slowing the development of treatment options and limiting the progression of the disease through its various stages.\n\nResearchers have identified that the inability of the brain to clear amyloid-beta (Aβ) and tau filaments is a core hallmark of progressive disease in the AD brain. One potential cause of this inability to clear the filaments is a lack of available energy, and the main cause is likely the mitochondria's natural reduction in the production of NAD+, the primary energy source for cellular respiration.\n\nRecently, naturally derived chemicals have moved to the forefront of research as the search for causes and cures moves forward. Many naturally derived molecules are showing good promise in the support of the mitochondria, including urolithin A (UA), a natural post-biotic produced by the gut microbiome after consuming pomegranates, nuts, and other berries, which has been shown to support control of symptoms associated with AD in both animal models and human neural cells.\n\nThis Phase II clinical trial seeks to evaluate the efficacy of UA in reducing levels of core AD biomarkers (including p-Tau217), biomarkers of non-specific processes involved in AD pathophysiology (such as neuroinflammation and oxidative stress), and biomarkers of autophagy\u002Fmitophagy function, and in slowing cognitive decline in patients with AD. This strategy lays the groundwork for the development of a novel dietary intervention strategy targeting mitochondria through nutritional supplementation.\n\nFor this study, Mitopure®\u002Furolithin A and its matching placebo have been supplied by Amazentis\u002FTimeline.",[67,72],{"label":68,"type":69,"description":51,"interventionNames":70},"Placebo","PLACEBO_COMPARATOR",[71],"Dietary Supplement: Placebo Control",{"label":73,"type":74,"description":51,"interventionNames":75},"1000 mg Mitopure®","EXPERIMENTAL",[76],"Dietary Supplement: Urolithin A",[78,83],{"type":79,"name":80,"description":81,"armGroupLabels":82,"otherNames":51},"DIETARY_SUPPLEMENT","Urolithin A","Softgels providing 1000 mg of Mitopure®\u002Furolithin A, taken orally once daily from day 1 and continuing for 48 weeks.",[73],{"type":79,"name":84,"description":85,"armGroupLabels":86,"otherNames":51},"Placebo Control","Matching placebo softgels, taken once daily from day 1 and continuing for 48 weeks.",[68],[88,92],{"name":89,"affiliation":90,"role":91},"Evandro Fei Fang-Stavem, PhD","Akershus University Hospital and University of Oslo","PRINCIPAL_INVESTIGATOR",{"name":93,"affiliation":94,"role":91},"Martin Vyhnálek, MD, PhD","Second Faculty of Medicine, Charles University",[96,101],{"name":97,"role":98,"phone":99,"phoneExt":51,"email":100},"Shuqin Cao, PhD","CONTACT","+47 67 96 00 00","shuqin.cao@medisin.uio.no",{"name":102,"role":98,"phone":103,"phoneExt":51,"email":104},"Thale Patrick-Brown","+47 23 07 00 00","d.j.patrick-brown@medisin.uio.no",[106],{"facility":94,"status":107,"city":108,"state":51,"zip":109,"country":110,"countryCode":51,"cosmosGeoPoint":111,"geoPoint":116,"contacts":117},"RECRUITING","Prague","150 06","Czechia",{"type":112,"coordinates":113},"Point",[114,115],14.42076,50.08804,{"lat":115,"lon":114},[118,121,124,126],{"name":93,"role":98,"phone":119,"phoneExt":51,"email":120},"+420 224 436 860","martin.vyhnalek@lfmotol.cuni.cz",{"name":122,"role":98,"phone":51,"phoneExt":51,"email":123},"Katerina Veverova, PhD","katerina.veverova@lfmotol.cuni.cz",{"name":122,"role":125,"phone":51,"phoneExt":51,"email":51},"SUB_INVESTIGATOR",{"name":127,"role":91,"phone":51,"phoneExt":51,"email":51},"Martin Vyhnalek, MD, PhD",{"type":91,"investigatorFullName":129,"investigatorTitle":130,"investigatorAffiliation":5,"oldNameTitle":51,"oldOrganization":51},"Evandro Fei Fang-Stavem","Principal Investigator",[132,134],{"name":133,"class":6},"Alzheimer's Association",{"name":135,"class":6},"Charles University, Czech Republic","100657637","the-effect-of-urolithin-a-mitopure-on-alzheimers-disease-100657637",false,"NCT07842146","The Effect of Urolithin A (Mitopure®) on Alzheimer's Disease","A Phase II Clinical Trial on the Effect of a Mitophagy Inducer Urolithin A on Alzheimer's Disease","Mito-AD","Inclusion Criteria:\n\nIN-1. Participants must be between 55 and 85 years of age at the time of inclusion.\n\nIN-2. Participants must meet the National Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria for Alzheimer's disease (AD)\n\nIN-3. Participants must have evidence of AD pathology, confirmed by either a positive amyloid PET imaging result or cerebrospinal fluid (CSF) biomarkers reflecting amyloid pathology (e.g., decreased Aβ42 levels or decreased Aβ42\u002F40 ratio, and increased levels of p-Tau181, and total Tau)\n\nIN-4. Participants must have a Mini-Mental State Examination (MMSE) score of ≥24.\n\nIN-5. Participants must have been on stable doses of FDA-approved AD medications (e.g., cholinesterase inhibitors) for at least 8 weeks prior to screening\n\nIN-6. Participants must possess adequate visual and auditory acuity to complete testing\n\nIN-7. Participants must speak fluent Czech.\n\nIN-8. Participants must have a reliable study partner.\n\nIN-9. Participants must have the ability to provide written consent to participate.\n\nIN-10. Participants must be capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol\n\nExclusion Criteria:\n\nEX-1. Participants will be excluded if they do not have clinically diagnosed AD.\n\nEX-2. Participants will be excluded if they have significant neurological conditions other than AD (e.g., Parkinson's disease, frontotemporal dementia, or vascular dementia), a history of head trauma with persistent neurological deficits, or baseline neuroimaging indicating cortical stroke or severe ischemic disease\n\nEX-3. Participants will be excluded if they have suffered from psychiatric conditions such as major depressive disorder (within the past year), bipolar disorder, or schizophrenia will be excluded\n\nEX-4. Participants will be excluded if they have had recent substance use disorder (past 2 years)\n\nEX-5. Participants will be excluded if they have unstable systemic illnesses including hepatic or renal failure\n\nEX-6. Participants will be excluded if they have decompensated diabetes\n\nEX-7. Participants will be excluded if they are taking medications with anticholinergic effects\n\nEX-8. Participants will be excluded if they are taking dietary supplements containing nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR)\n\nEX-9. Participants will be excluded if they have significant spinal disease complicating lumbar puncture or with anticoagulant therapy (only for the CSF group)\n\nEX-10. Participants will be excluded if they have participated in another investigational trial within the past 3 months or have medical conditions that could jeopardise their safety or affect study results, as judged by the investigator","ALL","55 Years","85 Years",{"count":148,"type":149},60,"ESTIMATED","INTERVENTIONAL",[152],"NA","The overall aim of MITO-AD is to evaluate if the nutritional supplement urolithin A is associated with favourable changes in Alzheimer's disease-related biomarkers, cognitive measures, and safety\u002Ftolerability outcomes in symptomatic patients with early-stage, biomarker-defined Alzheimer's disease. To do this, we will use two groups: one will be given standard care plus the food supplement urolithin A (the test group), and the other will be given just standard care plus a placebo (the control group). To measure potential differences between the groups, we will:\n\n* Do clinical and neuropsychological assessments at baseline and follow-up visits, with main biomarker sampling at baseline, week 24, and week 48. (Additional safety, tolerability, compliance, and questionnaire-based assessments will be performed during the study.)\n* Test blood samples from these patient groups for differences in various biomarkers to assess biological differences between them, and\n* Test cerebrospinal fluid (CSF) from a voluntary sub-cohort who will undergo CSF sampling at baseline and Week 4 to assess urolithin A exposure.\n\nN.B. Both groups will continue standard-of-care symptomatic Alzheimer's disease treatment as prescribed by the treating physician (where applicable). Standard of care may include acetylcholinesterase inhibitors and\u002For memantine. Participants receiving standard symptomatic Alzheimer's disease treatment must have been on a stable dose for at least 8 weeks prior to screening. Participants receiving anti-amyloid disease-modifying therapy will not be enrolled",[155,156,157],"Alzheimer's Disease (AD)","Early Alzheimer's Disease","Mild Cognitive Impairment Due to Alzheimer's Disease",[159,80,160],"Alzheimer's disease","Mitophagy","2026-10-07",{"date":163,"type":164},"2026-10-08","ACTUAL",{"date":166,"type":164},"2026-09-26",{"date":168,"type":149},"2028-10-15",{"name":5,"class":6},1]