A Nutritional Intervention for Body, Brain, and Longevity Effects (NIBBLE)

Official title

A Nutritional Intervention for Body, Brain, and Longevity Effects (NIBBLE) - A Randomized Open-label Intervention of the Fasting-mimicking Diet (FMD)

Overview

The study aims to evaluate the safety, feasibility, and preliminary efficacy of six-month fasting-mimicking (FMD) relative to Dietary Guidance intervention 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 consume a FMD for 5-days each month over a period of 6-months.

Detailed description

Participants assigned to the FMD arm will adhere to the diet for 5 days a month over a period of 6-months. The FMD diet is produced by L-Nutra and provides 1100 kcals on the 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. The Dietary Guidance Group will receive recommendations based on the Harvard Healthy Eating Plate.

The overarching hypothesis of the study is that FMD relative to dietary guidance will be safe and well-tolerated. It is also hypothesized that FMD will be associated with increases in cerebral blood flow. . This is a phase 2 single-site trial with a randomized, open label, parallel assignment design. To minimize bias, individuals evaluating the cognitive, research lab, and MRI outcomes will be blinded to the assigned intervention group.

The study will enroll 40 participants who will be randomized 1:1 to the fasting-mimicking diet (FMD) intervention versus the Dietary Guidance group with stratification for age and sex. The intervention period is 6-months. Study visits 2-7 occur the day after the participant completes five days of FMD for that cycle if assigned to the FMD group. Visits 2, 3, 5, and 6 will be completed via phone or secure video platform. The intervention period is followed by a 3-month observational follow-up period for both groups.

The study design will enable preliminary investigations of the efficacy of FMD relative to the Dietary Guidance group for cognition, ADRD blood biomarkers, epigenetic clock, and brain structure in function in middle-aged adults at elevated risk for Alzheimer's disease due to the APOE e4 genotype. As diet requires volitional activity, the study participants cannot be blinded. To minimize bias, the investigators evaluating cognitive, research labs, and MRI outcomes will be blinded to group assignments.

Interventions

• Dietary supplement FMD1 (LNT22-017-1)
  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.
• Behavioral Dietary Guidance
  Participants will receive established dietary guidance based on the Harvard Healthy Eating Plate.

Primary outcome measures

• Evaluate the safety of a six-month FMD intervention [Time frame: From pre- to post-treatment (Day 165 +/-8 days)]

Secondary outcome measures (2)

• Investigate the impact of the FMD intervention on cerebral blood flow relative to the Dietary Guidance Group [Time frame: From pre- to post-treatment (Day 165 +/-8 days)]
• Investigate the impact of the FMD intervention on cognition relative to the Dietary Guidance group. [Time frame: From pre- to post-treatment (Day 165 +/-8 days)]

Eligibility criteria

Inclusion criteria

• 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
• BMI 20-39kg/m2 (inclusive) at screening
• On a stable medication regimen for at least 3 months.

Exclusion criteria

• 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.
• Current adherence or adherence within the past 3 months to a specialized diet (e.g. ketogenic, paleo, intermittent fasting, raw food, vegan)
• Food allergies (e.g. dairy, eggs, fish/shellfish, peanuts, tree nuts, soy, wheat, sesame, corn)
• Diagnosis of mild cognitive impairment or dementia; use of an FDA-approved medication for Alzheimer's disease; MoCA<23
• Diabetes (hbA1c >6.5%) or anti-diabetic medications
• History of gastric bypass;
• Inflammatory bowel disease
• Small or large bowel resection
• Subjects with recent weight loss (>5%), use of weight loss medication, participated in a weight loss program in the past 3 months
• Use of immune suppression drugs;
• Contraindication for study foods (special food needs and allergy);
• Women who are pregnant, lactating, or trying to conceive
• Alcohol dependency (alcohol intake greater than two drinks per day for women and three drinks per day for men)
• Current smoker or tobacco use within 3 months.
• Active malignant cancer or history of malignancy within the last 1 yea1s (except non-melanoma skin cancer)
• Serious psychiatric disorders such as schizophrenia, bipolar disorder, eating disorders
• Persons with allergy to animal dander or animal-instigated asthma

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

United States · 1 center

• Cedars Sinai Medical Center — Los Angeles

Identifiers

NCT: NCT06682767 · STUDY00003359

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗