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
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Parallel
Urolithin A
Dietary supplementSoftgels providing 1000 mg of Mitopure®/urolithin A, taken orally once daily from day 1 and continuing for 48 weeks.
Placebo Control
Dietary supplementMatching 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.
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.
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.
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.
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
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University Hospital, Akershus
Lead sponsor
Alzheimer's Association
Collaborator
Charles University, Czech Republic
Collaborator
