An interventional study of Urolithin A and Placebo Control in Alzheimer's Disease (AD), Early Alzheimer's Disease and Mild Cognitive Impairment Due to Alzheimer's Disease, sponsored by University Hospital, Akershus. Recruiting at 1 site in Czechia. Open to participants aged 55 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by University Hospital, Akershus · Not applicable, Interventional, and Supportive care
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/tolerability 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.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/or 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
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.
Researchers 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.
Recently, 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.
This 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/mitophagy 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.
For this study, Mitopure®/urolithin A and its matching placebo have been supplied by Amazentis/Timeline.
3,965 studies on the registry are indexed under Alzheimer Disease; 926 are open to participants now.
This study's planned enrollment of 60 is below the median of 70 across 3,019 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →University Hospital, Akershus is the lead sponsor of 125 studies on the registry; 28 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
IN-1. Participants must be between 55 and 85 years of age at the time of inclusion.
IN-2. Participants must meet the National Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria for Alzheimer's disease (AD)
IN-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 Aβ42/40 ratio, and increased levels of p-Tau181, and total Tau)
IN-4. Participants must have a (MMSE) score of ≥24.
IN-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
IN-6. Participants must possess adequate visual and auditory acuity to complete testing
IN-7. Participants must speak fluent Czech.
IN-8. Participants must have a reliable study partner.
IN-9. Participants must have the ability to provide written consent to participate.
IN-10. Participants must be capable of giving signed as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
Exclusion Criteria:
EX-1. Participants will be excluded if they do not have clinically diagnosed AD.
EX-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
EX-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
EX-4. Participants will be excluded if they have had recent substance use disorder (past 2 years)
EX-5. Participants will be excluded if they have unstable systemic illnesses including hepatic or renal failure
EX-6. Participants will be excluded if they have decompensated diabetes
EX-7. Participants will be excluded if they are taking medications with anticholinergic effects
EX-8. Participants will be excluded if they are taking dietary supplements containing nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR)
EX-9. Participants will be excluded if they have significant spinal disease complicating lumbar puncture or with anticoagulant therapy (only for the CSF group)
EX-10. Participants will be excluded if they have participated in another trial within the past 3 months or have medical conditions that could jeopardise their safety or affect study results, as judged by the investigator
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Dietary Supplement: Placebo Control
Dietary Supplement: Urolithin A
Softgels providing 1000 mg of Mitopure®/urolithin A, taken orally once daily from day 1 and continuing for 48 weeks.
Matching placebo softgels, taken once daily from day 1 and continuing for 48 weeks.
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.
Time frame: Baseline and Week 48.
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.
Time frame: Baseline, and then at Week 24 and Week 48.
Mean difference in mitophagy/autophagy 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.
Time frame: Baseline, and then week 24 and week 48.
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 / greater oxidative damage.
Time frame: Baseline, and then at week 24 and week 48.
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
Time frame: Baseline, and then week 24 and week 48.
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.
Time frame: Baseline, and then Week 24 and Week 48.
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.
Time frame: Baseline, and then at Week 24 and Week 48.
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.
Time frame: Baseline, and then at Week 24 and Week 48.
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/incapacity, 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.
Time frame: From baseline through Week 48, including scheduled safety/tolerability assessments at Weeks 12, 24, 36, and 48.
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.
Time frame: Throughout the study (mobile app), and at participant control visits at Weeks 12, 24, 36, and 48.
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 / CNS exposure.
Time frame: Baseline and week 4.
Plan to share: Yes — Yes, there is a plan to make IPD and related data dictionaries available to other researchers upon reasonable request.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: De-identified individual participant data and related supporting materials may be made available upon reasonable request after completion of the study and publication of the main results, subject to applicable ethical approvals, GDPR requirements, institutional policies, data use agreements, and any relevant confidentiality restrictions.
Access criteria: All reasonable requests for access will be approved. Data will be transferred using secure protocols or via links to the OSF for the project, once available.
No publications or documents are linked to this record.
Started Sep 2026 (actual). Primary completion is estimated for Oct 2028, 24 months after the start.
Of 882 non-industry interventional studies with no phase under Alzheimer Disease, half reached primary completion within 30 months of starting (the median), counting those still running; a quarter within 15 and three quarters within 51. This study's planned 24 months is below that.
Counting every sponsor, half of 959 studies reached it within 29 months; a quarter within 15 and three quarters within 51.
Start moved once since we started tracking on Sep 25, 2026: Oct 2026 → Sep 2026, on Oct 8, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Urolithin A Supplement
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