Clinical trial NCT06682767: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cerebral Blood Flow
APOE 4
Keywords: APOE 4
prevention
alzheimer&#39;s disease
nutritition
fasting mimicking diet
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
First posted: 2024-11-12
Enrollment: 60
Sex: ALL
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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\&#39;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

Primary outcomes:
measure: Investigate the impact of the FMD intervention on cerebral blood flow relative to normal diet
timeFrame: From enrollment to end of study (Day 251 +/-7 days)
Secondary outcomes:
measure: Evaluate the safety of a six-month FMD intervention
timeFrame: From enrollment to end of study (Day 251 +/-7 days)
measure: Investigate the impact of the FMD intervention on cognition relative to normal diet
timeFrame: From enrollment to end of study (Day 251 +/-7 days)
Other outcomes:
measure: Examine the impact of FMD relative to normal diet on ADRD blood-based biomarkers
timeFrame: From enrollment to end of study (Day 251 +/-7 days)
measure: Evaluate the efficacy of FMD relative to normal diet for modulating autophagic flux
timeFrame: From enrollment to end of study (Day 251 +/-7 days)
measure: Evaluate the efficacy of FMD relative to normal diet for modulating metabolic parameters
timeFrame: From enrollment to end of study (Day 251 +/-7 days)
measure: Examine the impact of FMD on systemic markers of inflammation through physiological paramaters.
timeFrame: From enrollment to end of study (Day 251 +/-7 days)
measure: Evaluate the efficacy of FMD relative to normal diet for modulating metabolic parameters
timeFrame: From enrollment to end of study (Day 251 +/-7 days)
measure: Evaluate the efficacy of FMD relative to normal diet for modulating metabolic parameters
timeFrame: From enrollment to end of study (Day 251 +/-7 days)
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Mitzi Gonzales, PhD
role: PRINCIPAL_INVESTIGATOR
References: