Alzheimer's Disease (AD)Mito-ADNCT07842146
The Effect of Urolithin A (Mitopure®) on Alzheimer's Disease
A study testing Urolithin A in people with Alzheimer's Disease (AD) and Early Alzheimer's Disease, run by University Hospital, Akershus at 1 site in Czechia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer's Disease (AD), Early Alzheimer's Disease, Mild Cognitive Impairment Due to Alzheimer's Disease
- What is being tested?
- Urolithin A
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteCzechia
- Study dates
- 26 Sep 2026to 15 Oct 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 Mini-Mental State Examination (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
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- 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 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
Who cannot join
- 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
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- 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 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Czechia1 site, 1 recruiting
- Recruiting
Second Faculty of Medicine, Charles University
Prague, 150 06
Martin Vyhnálek, MD, PhD, +420 224 436 860, martin.vyhnalek@lfmotol.cuni.cz
Katerina Veverova, PhD, katerina.veverova@lfmotol.cuni.cz
About this study
Official title: A Phase II Clinical Trial on the Effect of a Mitophagy Inducer Urolithin A on Alzheimer's Disease
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:
- 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.)
- Test blood samples from these patient groups for differences in various biomarkers to assess biological differences between them, and
- 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.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
Read the detailed description
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.
- Conditions
- Alzheimer's Disease (AD), Early Alzheimer's Disease, Mild Cognitive Impairment Due to Alzheimer's Disease
- Being tested
- Urolithin A, Placebo Control
- Keywords
- Alzheimer's disease, Urolithin A, Mitophagy
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Urolithin ADietary supplement
Softgels providing 1000 mg of Mitopure®/urolithin A, taken orally once daily from day 1 and continuing for 48 weeks.
Placebo ControlDietary supplement
Matching placebo softgels, taken once daily from day 1 and continuing for 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Dietary Supplement: Placebo Control |
| 1000 mg Mitopure® | Experimental | Not described Receives: Dietary Supplement: Urolithin A |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 48.
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and week 4.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2026
- Study start26 Sep 2026
- Primary completion15 Oct 2028 (estimated)
- Study completion15 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's Disease (AD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A double-blind, single centre, randomised, placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Akershus
- Sponsor type
- University, hospital or other
- Collaborators
- Alzheimer's Association, Charles University, Czech Republic
- Responsible party
- Principal investigator, Evandro Fei Fang-Stavem, University Hospital, Akershus
- Investigators
- Evandro Fei Fang-Stavem, PhD, Principal investigator, Akershus University Hospital and University of OsloMartin Vyhnálek, MD, PhD, Principal investigator, Second Faculty of Medicine, Charles University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07842146
- Sponsor's protocol ID
- 967952
- Acronym
- Mito-AD
- Status last verified
- Oct 2026
- First submitted
- 5 Aug 2026
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Yes, there is a plan to make IPD and related data dictionaries available to other researchers upon reasonable request.