Primary objective | Primary endpoint |
To evaluate the efficacy of rapamycin treatment in patients with early-stage Alzheimer’s disease | Change-from-baseline for: • [18F]FDG brain uptake, measured with PET |
Secondary endpoints | |
Change-from-baseline for: • MoCA total score • CSF levels of amyloid beta, p-tau, and t-tau • Cerebral blood flow, measured with MRI using a non-invasive pseudo-continuous arterial spin-labeling sequence | |
Exploratory endpoints | |
• Physical performance: ◦ Timed 10 m walking test ◦ Timed 10 m dual-task test ◦ 30 s chair stand test ◦ Hand strength • Neuropsychological cognitive testing using: ◦ Rey Auditory Verbal Learning Test (learning and delayed recall) ◦ Rey–Osterrieth Complex Figure ◦ Hagman test ◦ Trail Making Test A + B ◦ Wechsler Adult Intelligence Scale, 4th edition coding subtest to assess processing speed/attention | |
Secondary objectives | |
To evaluate pharmacokinetic properties of intermittent dosing of rapamycin | Whole blood measurements of rapamycin concentration: ◦ Cmax ◦ Ctrough ◦ Area under the curve |
To evaluate the safety and tolerability of rapamycin when intermittently dosed against AD | Safety and tolerability as measured by incidence of AEs/SAEs; clinical laboratory test data; vital signs |
Exploratory objectives | |
To evaluate a general “geroprotective” effect of rapamycin treatment, by measuring changes in age-related tissue pathologies, such as: • Periodontal associated inflammation • Retinal degeneration • Atherosclerosis in large arteries • Heart function • Myocardial inflammation • Bone mineral density | Change-from-baseline for: • Periodontal oedema and bone remodeling, measured using MRI and CT • Thickness and thickness ratios of retinal nerve fiber layers in the macula and optic disc, measured using OCT • Pulse wave velocity in the aorta, measured using MRI • [18F]FDG uptake in atherosclerotic plaques in large arteries • Heart function (including, but not limited to: diastolic function, microvascular function, myocardial-volume and strain), measured with MRI • Bone mineral density in lumbar vertebrae, measured using qCT |