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
• 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
• 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