A Nutritional and Pharmacological Intervention for Body, Brain, and Longevity Effects (NIBBLE)
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age45-65
SponsorCedars-Sinai Medical Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 45-65 years at screening
Carrier of at least one copy of the APOE e4 allele
Disqualifiers
Has any medical disease or condition that, in the opinion of the principal investigator (PI) or appropriate study personnel, precludes study participation* (*Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial);
Significant depression (PHQ-9>9) or generalized anxiety (GAD-7>9)
Diagnosis of a significant neurological condition such as multiple sclerosis, epilepsy, Parkinson's disease, major stroke
Contraindications to MRI such as claustrophobia, cardiac pacemaker, etc.
Trial design
Design model
Parallel
Treatments tested in this trial
FMD1 (LNT22-017-1)
Dietary supplementFMD 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.
Rapamycin
DrugParticipants randomly assigned to the rapamycin arm will take 1 mg of rapamycin daily for approximately 8 weeks..
Placebo
DrugParticipants randomly assigned to the placebo arm will take one placebo pill daily for approximately 8 weeks.
Treatment groups
60 Participants
are divided into 3 treatment groupsGroup A: FMD - InterventionExperimental treatment 1 intervention
Group B: RapamycinExperimental treatment 1 intervention
Group C: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
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)Secondary outcomes
1
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)2
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)Other outcomes
1
Examine and compare impact of FMD and rapamycin relative to placebo on ADRD blood-based biomarkers
Endpoint: Circulating levels of phosphorylated tau 217 (p-tau 217), neurofilament light (NFL), and glial fibrillary acidic protein (GFAP). The same unit of measurement applies for all - pg/ml.
Time frame
From pre- to post-treatment (Day 72 +/- 5 days)2
Evaluate and compare the efficacy of FMD and rapamycin relative to placebo for modulating autophagic flux
Endpoint: Autophagic flux in PBMCs and tissue (optional) Autophagy related gene expression. Both have the same unit of measurement as arbitrary units.
Time frame
From pre- to post-treatment (Day 72 +/- 5 days)3
Evaluate and compare the efficacy of FMD and rapamycin relative to placebo for modulating insulin growth factor-1
Endpoint: insulin growth factor 1 (unit of measure is ng/ml)
Time frame
From pre- to post-treatment (Day 72 +/- 5 days)4
Examine and compare the impact of FMD and rapamycin relative to placebo on systemic markers of inflammation through physiological parameters.
Endpoint: Proteomic expression of pro-inflammatory markers Pro-inflammatory markers are IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, which are all measured in pg/ml.
Time frame
From pre- to post-treatment (Day 72 +/- 5 days)Sponsors and contacts
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Source ClinicalTrials.gov
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