The study aims to evaluate the safety, feasibility, and preliminary efficacy of the fasting-mimicking diet (FMD) or low-dose daily rapamycin treatment relative to a matched placebo control group when administered over 8 weeks in middle-aged adults at elevated risk for Alzheimer's disease due to the apolipoprotein (APOE) ε4 allele. Participants randomly assigned to the FMD intervention will adhere to FMD for 5-days over three cycles for a period of approximately 8 weeks. Participants randomly assigned to the rapamycin and placebo groups will take 1 mg of rapamycin or a matched placebo pill daily for approximately 8 weeks.
Participants assigned to the FMD arm will adhere to the diet for 5 days over three cycles for a period of 8 weeks. The FMD diet is produced by L-Nutra and provides 1100 kcals on day 1 and 800 kcals on days 2-5. The diet consists of ingredients which are Generally Regarded As Safe (GRAS) selected for their fasting mimicking properties. Participants randomized to the rapamycin group will receive 1 mg rapamycin daily for 8 weeks and those in the placebo arm will take one matched placebo pill daily for 8 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
60
FMD is a plant-based ketogenic diet that provides essential nutrients while maintaining hypo-caloric content. FMD is administered cyclically with 3-5 consecutive days of the diet followed by resumption of normal eating.
Participants randomly assigned to the rapamycin arm will take 1 mg of rapamycin daily for approximately 8 weeks..
Participants randomly assigned to the placebo arm will take one placebo pill daily for approximately 8 weeks.
Cedars Sinai Medical Center
Los Angeles, California, United States
Evaluate and compare the safety of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group
Endpoint: Number of adverse events in the intervention groups relative to the placebo group.
Time frame: From pre- to post-treatment (Day 72 +/- 5 days)
Investigate the effect of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group.
Endpoint: Cerebral blood flow - Cerebral blood flow will be assessed through brain magnetic resonance imaging arterial spin labeling sequence.
Time frame: From pre- to post-treatment (Day 72 +/- 5 days)
Investigate and compare the impact of the FMD and rapamycin interventions on cognition relative to the placebo group.
NIH Toolbox Flanker and Pattern Comparison Tests and the Mayo Preclinical Alzheimer's Cognitive Composite. The NIH Toolbox assessments are measured through scaled scores (T-scores), which range from 20-80 with higher scores indicating better outcomes. The Mayo Preclinical Alzheimer's Cognitive Composite is also measured using a standardized score (Z-score) with mean of 0 and a standard deviation of 1. Higher scores indicate better performance.
Time frame: From pre- to post-treatment (Day 72 +/- 5 days)
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