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

NCT ID: NCT06682767

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-30
• Study Completion Date: 2026-11-30

Brief Summary

The study aims to evaluate the safety, feasibility, and efficacy of six-month fasting-mimicking (FMD) intervention in middle-aged adults at elevated risk for Alzheimer's disease due to the apolipoprotein (APOE) ε4 allele. Participants randomly assigned to the active 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 overarching hypothesis of the study is that the dietary intervention will be safe and well-tolerated. 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 60 participants who will be randomized 1:1 to the fasting-mimicking diet (FMD) intervention versus normal diet 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. The intervention period if followed by a 3-month observational follow-up period.

The study design will enable investigations of the efficacy of FMD relative to normal diet for cognition, ADRD blood biomarkers, 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.

Conditions

Cerebral Blood Flow; APOE 4

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

FMD - Intervention

Participants in the FMD group will be asked to refrain from consuming any calorie-containing foods or drinks other than the provided study foods/drinks during the designated intervention days each month.

Group Type: EXPERIMENTAL

FMD1 (LNT22-017-1)

Intervention Type: DIETARY_SUPPLEMENT

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.

Normal Diet - Control

Participants in the normal diet group will be asked to consume their regular diet.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, aged 45-65 years at screening

4. Carrier of at least one copy of the APOE e4 allele

5. BMI 20-39kg/m2 (inclusive) at screening

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 greater than 9) or generalized anxiety (GAD-7 greater than 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 less than 23
• Diabetes (hbA1c greater than 6.5%) or anti-diabetic medications
• History of gastric bypass;
• Inflammatory bowel disease
• Small or large bowel resection
• Subjects with recent weight loss (greater than 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 years (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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Mitzi Gonzales

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mitzi Gonzales, PhD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mitzi Gonzales, PhD

Role: CONTACT

mitzi.gonzales@cshs.org

424-315-0228

Sara Espinoza, MD

Role: CONTACT

sara.espinoza@cshs.org

210-310-5859

Facility Contacts

Mitzi Gonzales, PhD

Role: primary

mitzi.gonzales@cshs.org

424-315-0228

Sara Espinoza, MD

Role: backup

sara.espinoza@cshs.org

Other Identifiers

STUDY00003359

Identifier Type: -

Identifier Source: org_study_id