The Effect of Urolithin A (Mitopure®) on Alzheimer's Disease

NCT07842146 | Not Yet Recruiting DMC

• 1 other identifier: 967952
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Alzheimer's Disease (AD); Early Alzheimer's Disease; Mild Cognitive Impairment Due to Alzheimer's Disease

Keywords

Alzheimer's disease; Urolithin A; Mitophagy

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (10)

• Mean difference from baseline in GFAP in patients receiving Urolithin A versus placebo

  Baseline, and then at Week 24 and Week 48.

• Mean difference in mitophagy/autophagy biomarkers in patients receiving urolithin A versus placebo

  Baseline, and then week 24 and week 48.

• Change from baseline in blood lipofuscin-like pigment relative fluorescence intensity

  Baseline, and then at week 24 and week 48.

• Change from baseline in cellular reactive oxygen species fluorescence intensity in erythrocytes and plasma.

  Baseline, and then week 24 and week 48.

• Change from baseline in mitochondrial reactive oxygen species fluorescence intensity in PBMCs

  Baseline, and then Week 24 and Week 48.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Dietary Supplement: Placebo Control

1000 mg Mitopure®

EXPERIMENTAL

Dietary Supplement: Urolithin A

Interventions

Urolithin A DIETARY_SUPPLEMENT

Softgels providing 1000 mg of Mitopure®/urolithin A, taken orally once daily from day 1 and continuing for 48 weeks.

1000 mg Mitopure®

Placebo Control DIETARY_SUPPLEMENT

Matching placebo softgels, taken once daily from day 1 and continuing for 48 weeks.

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Alzheimer's Association: collaborator
• University Hospital, Akershus: lead
• Charles University, Czech Republic: collaborator

Study Sites (1)

Second Faculty of Medicine, Charles University

Prague, 150 06, Czechia

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Evandro Fei Fang-Stavem, PhD

  Akershus University Hospital and University of Oslo

  PRINCIPAL INVESTIGATOR

• Martin Vyhnálek, MD, PhD

  Second Faculty of Medicine, Charles University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shuqin Cao, PhD

CONTACT

+47 67 96 00 00; shuqin.cao@medisin.uio.no

Thale Patrick-Brown

CONTACT

+47 23 07 00 00; d.j.patrick-brown@medisin.uio.no

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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/randomisation contact if required for participant safety.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A double-blind, single centre, randomised, placebo-controlled trial

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: September 25, 2026
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): October 15, 2028
• Study Completion (Estimated): October 15, 2028
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, 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.

Locations

CZ (1)