A Nutritional and Pharmacological Intervention for Body, Brain, and Longevity Effects (NIBBLE) - A Randomized Open-label Intervention of the Fasting-mimicking Diet (FMD) and Rapamycin (NIBBLE)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Evaluate and compare the safety of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The rapamycin and matched placebo groups will be blinded to assignment (rapamycin vs matched placebo). As diet requires volitional activity, the study participants assigned to this aim cannot be blinded. To minimize bias, the investigators evaluating cognitive, research labs, and MRI outcomes will be blinded to all group assignments.
入排标准
- 年龄范围
- 45 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •For females: Post-menopausal status or use of highly effective contraception.
排除标准
- •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
- •Women who are on hormone replacement therapy
- •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
- •Required use of drugs that affect cytochrome P450 3A4 or alter cerebral blood flow (see Appendix 1 for tables of excluded medications)
- •Current or chronic liver, kidney, cardiac, or pulmonary diseases
- •Untreated hypertriglyceridemia (fasting triglycerides > 300 mg/dl)
- •Poorly controlled blood pressure (systolic BP > 160 or diastolic BP > 100 mmHg
研究组 & 干预措施
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.
干预措施: FMD1 (LNT22-017-1) (Dietary Supplement)
Placebo
Participants randomly assigned to the placebo arm will take one placebo pill daily for approximately 8 weeks.
干预措施: Placebo (Drug)
Rapamycin
Participants randomly assigned to the rapamycin arm will take 1 mg of rapamycin daily for approximately 8 weeks.
干预措施: Rapamycin (Drug)
结局指标
主要结局
Evaluate and compare the safety of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group
时间窗: From pre- to post-treatment (Day 72 +/- 5 days)
Endpoint: Number of adverse events in the intervention groups relative to the placebo group.
Evaluate the safety of a six-month FMD intervention
时间窗: From pre- to post-treatment (Day 165 +/-8 days)
Endpoint: Number of adverse events in the intervention group relative to the Dietary Guidance group
次要结局
- Investigate the effect of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group.(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.(From pre- to post-treatment (Day 72 +/- 5 days))
- Investigate the impact of the FMD intervention on cerebral blood flow relative to the Dietary Guidance Group(From pre- to post-treatment (Day 165 +/-8 days))
- Investigate the impact of the FMD intervention on cognition relative to the Dietary Guidance group.(From pre- to post-treatment (Day 165 +/-8 days))
研究者
Mitzi Gonzales
Principal Investigator
Cedars-Sinai Medical Center