Ecosystem Nourishment for Gut Restoration After Fecal Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Difference in DunedinPACE
研究概览
简要总结
The purpose of this study is to test whether young-donor fecal microbiome transplantation (FMT) and a fermented, plant-rich high-fiber, microbiome rejuvenating diet (MRD) reduce inflammatory and biological aging markers. Participants (≥40 years) will be randomized (1:1:1:1) for 8 weeks with 4-week follow-up to: (A) diet alone, (B) FMT alone, (C) diet + FMT, or (D) Placebo FMT. We will use rigorously screened young and healthy FMT donors and encapsulated delivery. Outcomes include change from baseline to end of dietary intervention (week 8) in markers of aging and inflammation. Secondary outcomes include defining microbiome engraftment/diversity/function, key metabolites, diet adherence, and quality-of-life.
详细描述
For this study, the research participant will receive a once daily oral dose of healthy young FMT and diet modification to increase fiber and fermented food consumption. Throughout the study's duration, the participant will provide stool, blood and urine samples as well as a series of health questionnaires to track the impact of the intervention.
*PROTOCOL OVERVIEW* The study will begin with the selection of possible participants through the samples collected through the Stanford Microbiome Bank (IRB 85544), the participants identified will be contacted through the appropriate channels and asked to complete a short online questionnaire if interested in continuing with being a part of the protocol.After completing the questionnaire, those selected will be contacted via phone to schedule an in person appointment in the Clinical and Translational Research Unit (CTRU). During this appointment, the study team will obtain informed consent and one stool sample. Their initial stool sample will be sent outside Stanford for microbiome composition analysis which will determine if the participant is a good candidate for the protocol.
After enrollment in the protocol, the participants will be randomized in a 1:1:1:1 ratio to one of four study arms: Placebo, placebo + diet, FMT no diet, or FMT + diet. Those randomized to one of the FMT groups will be instructed to take a single oral dose of young FMT (4 capsules) for two weeks, and those randomized to a diet arm will have an initial appointment with the study's dietitian to establish a microbiome rejuvenating diet (MRD) starting with a one week ramp up period and continued for a total of 8 weeks. The main factors incorporated into the MRD will be ~3 servings/day fermented foods and ≥30-40 g/day or +20g fiber(plant-based whole food), 5g of resistant starch supplements and 5g of psyllium husk.
Throughout their enrollment in the protocol, the participants will provide stool samples weekly for analysis and complete general health and lifestyle questionnaires to assess protocol adherence and any changes in their health status. On weeks 0, 2, 4, 8 & 12 participants will be asked to give a blood, urine and stool sample for further analysis and to complete a Nutrition Data System for Research (NDSR) questionnaire; stool is additionally collected at Week 6.
All patient samples will be coded and stored in Stanford facilities for further processing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Care Provider)
盲法说明
In addition to the parties designated in the structured masking fields, the study biostatistician and data analysts will remain masked to treatment allocation until database lock. Laboratory personnel processing and analyzing biological samples (e.g., stool, blood) will be masked to arm assignment.
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Able and willing to provide written informed consent prior to completion of any study procedures.
- •Age ≥40 years at the time of consent.
- •In generally good health, as determined by medical history, medication review, and investigator assessment.
- •Willing and able to comply with all study procedures, assessments, and study-related restrictions for the duration of participation.
- •Willing to adhere to the study's lifestyle considerations for the duration of the study (maintain usual diet unless assigned to the diet arm; maintain usual physical activity; avoid non-essential systemic antibiotics; avoid probiotic/prebiotic/synbiotic supplements).
- •Willing and able to attend all required in-person study visits at Stanford University and complete remote assessments, if applicable.
排除标准
- •Moderate or severe irritable bowel syndrome (IBS).
- •Current or prior diagnosis of inflammatory bowel disease (IBD), including ulcerative colitis, Crohn's disease, or indeterminate colitis.
- •Active gastrointestinal disease, including infectious gastroenteritis, colitis, gastritis, recurrent Clostridioides difficile infection, untreated Helicobacter pylori infection, or clinically significant malabsorption disorders (e.g., celiac disease).
- •Major gastrointestinal surgery within the past 5 years (excluding cholecystectomy and appendectomy), or history of major bowel resection at any time.
- •Body mass index (BMI) ≥40 kg/m².
- •Diabetes mellitus.
- •Hyperthyroidism or uncontrolled hypothyroidism.
- •Clinically significant renal disease.
- •Clinically significant hepatic disease or significant liver enzyme abnormalities.
- •Clinically significant cardiovascular disease.
- •Autoimmune or systemic inflammatory disease.
- •Current malignancy or history of malignancy within the past 5 years, excluding adequately treated non-melanoma skin cancer.
- •Current use of immunosuppressive medications, including systemic corticosteroids, thiopurines, methotrexate, calcineurin inhibitors, biologic agents, or other immunosuppressive therapies.
- •Receipt of fecal microbiota transplantation (FMT) within the previous 12 months.
- •Use of systemic antibiotic therapy within 30 days prior to enrollment or anticipated antibiotic use during the study period.
- •Use of probiotic supplements, prebiotic supplements, synbiotics, or live microbial therapeutics within 30 days prior to enrollment.
- •Current use or use within the previous 6 months of medications prescribed primarily for weight loss.
- •Current use of medications known to significantly affect body weight unless the medication and dose have remained stable for at least 6 months prior to enrollment.
- •Neurodevelopmental, psychiatric, neurological, or neuromuscular disorders that, in the opinion of the investigator, may impair the participant's ability to provide informed consent, comply with study procedures, or complete study assessments.
- •Current diagnosis of schizophrenia, bipolar disorder, or other severe psychiatric illness that may interfere with study participation.
- •Current substance use disorder.
- •Current smoking or nicotine use, including cigarettes, cigars, electronic cigarettes, vaping products, or nicotine replacement therapy.
- •History of anaphylaxis or severe allergic reaction to study-related dietary components.
- •Planned major dietary change, initiation of a structured weight-loss program, or initiation of a specialized therapeutic diet during the study period.
- •Concurrent participation in another interventional clinical trial.
- •Any other medical, psychiatric, or social condition that, in the opinion of the investigator, could compromise participant safety, study compliance, or interpretation of study outcomes.
- •Pregnancy or breastfeeding
- •Known immunodeficiency state, including HIV infection, primary immunodeficiency, active hematologic or solid-organ malignancy under treatment, or other clinically significant immunocompromise, independent of medication use.
- •Dysphagia or any condition impairing the ability to swallow oral capsules.
研究组 & 干预措施
FMT and Diet intervention
Participants will receive a once daily dose (4 pills) of young donor fecal microbiome transplant (FMT) for two weeks and a microbiome rejuvenating diet (MRD) intervention for 8 weeks. The dietary intervention consists of dietitian-guided increase to ~3 servings/day fermented foods and ≥30-40 g/day or +20g fiber(plant-based whole food) and 5g of resistant starch and 5g of psyllium husk supplements over 8 weeks.
干预措施: Fecal Microbiota Transplant Capsules (Drug)
FMT and Diet intervention
Participants will receive a once daily dose (4 pills) of young donor fecal microbiome transplant (FMT) for two weeks and a microbiome rejuvenating diet (MRD) intervention for 8 weeks. The dietary intervention consists of dietitian-guided increase to ~3 servings/day fermented foods and ≥30-40 g/day or +20g fiber(plant-based whole food) and 5g of resistant starch and 5g of psyllium husk supplements over 8 weeks.
干预措施: Microbiome Rejuvenating Diet (Behavioral)
FMT
Participants will receive a once daily dose of young donor FMT for two weeks.
干预措施: Fecal Microbiota Transplant Capsules (Drug)
Placebo FMT and diet
Participants receive placebo pills that are identical in shape size and feel to the active therapeutic daily for 2 weeks and will comply with a microbiome rejuvenating diet (MRD) for 8 weeks. The dietary intervention consists of dietitian-guided increase to ~3 servings/day fermented foods and ≥30-40 g/day or +20g fiber(plant-based whole food) and 5g of resistant starch and 5g of psyllium husk supplements over 8 weeks.
干预措施: Microbiome Rejuvenating Diet (Behavioral)
Placebo FMT and diet
Participants receive placebo pills that are identical in shape size and feel to the active therapeutic daily for 2 weeks and will comply with a microbiome rejuvenating diet (MRD) for 8 weeks. The dietary intervention consists of dietitian-guided increase to ~3 servings/day fermented foods and ≥30-40 g/day or +20g fiber(plant-based whole food) and 5g of resistant starch and 5g of psyllium husk supplements over 8 weeks.
干预措施: Placebo Fecal Microbiota Transplantation (Other)
Placebo FMT
Participants receive placebo pills that are identical in shape size and feel to the active therapeutic daily for 2 weeks
干预措施: Placebo Fecal Microbiota Transplantation (Other)
结局指标
主要结局
Difference in DunedinPACE
时间窗: Baseline and 8 weeks
Difference in the 8-week change from baseline in DunedinPACE among the four randomized groups (FMT + MRD, FMT alone, MRD + placebo FMT, and placebo FMT), assessed by DNA methylation analysis of whole blood. DunedinPACE is a DNA methylation biomarker that quantifies the pace of biological aging, reported as a rate of biological aging per chronological year; higher values indicate a faster pace of aging and lower values indicate a slower pace.
次要结局
- Difference in High-Sensitivity C-Reactive Protein (hsCRP)(Baseline and 8 weeks)
- Difference in Epigenetic Age(Baseline and 8 weeks)
- Difference in Telomere Length(Baseline and 8 weeks)
- Difference in Gut Microbial Alpha Diversity(Baseline and 8 weeks)
- Difference in Interleukin-6 (IL-6)(Baseline and 8 weeks)
- Difference in Growth Differentiation Factor-15 (GDF-15)(Baseline and 8 weeks)
- Difference in Cytokines and Inflammatory Proteins(Baseline and 8 weeks)
- Difference in Gut Microbiome Composition(Baseline and 8 weeks)
- Difference in Gut Microbial Beta Diversity(Baseline and 8 weeks)
- Difference in Gut Microbiome Functional Capacity(Baseline and 8 weeks)
- Engraftment of Donor-Derived Microbial Strains(Baseline, 8 weeks, and 12 weeks)
- Difference in Metabolomic Profiles(Baseline and 8 weeks)
- Difference in Grip Strength(Baseline and 8 weeks)
- Difference in Timed Up and Go (TUG)(Baseline and 8 weeks)
- Difference in Cognitive Function, Mini-Mental State Examination (MMSE)(Baseline and 8 weeks)
- Difference in Cognitive Function, Montreal Cognitive Assessment (MoCA)(Baseline and 8 weeks)
- Difference in Physical Function(Baseline and 8 weeks)
- Difference in Fatigue(Baseline and 8 weeks)
- Difference in Frailty(Baseline and 8 weeks)
- Difference in Weight(Baseline and 8 weeks)
- Difference in Body Mass Index (BMI)(Baseline and 8 weeks)
- Difference in Systolic Blood Pressure(Baseline and 8 weeks)
- Difference in Diastolic Blood Pressure(Baseline and 8 weeks)
- Difference in Dietary Fiber Intake(Baseline and 8 weeks)
- Difference in Fermented Food Intake(Baseline and 8 weeks)
- Incidence of Treatment-Emergent Adverse Events(Informed consent through 12 weeks)
- Difference in Gastrointestinal and Systemic Tolerability Symptom Scores(Baseline and 8 weeks)
研究者
Sean Spencer
Assistant Professor of Medicine; Medical Director of Microbiome Diagnostics and Therapeutics
Stanford University