Effect of Gut Microbiome Intervention on Aging Via Oral FMT

Early Phase 1

Not yet recruiting

• Conditions: Frailty; Aging
• Interventions: Other: Placebo capsules; Biological: FMT capsules

• Registration Number: NCT05598112
• Lead Sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital

Brief Summary

A severe public health issue facing global population is aging. Increasing preclinical and clinical data indicate the contribution of gut microbiome on aging and aging-related diseases such as cardiovascular disease, Alzheimer Disease, and diabetes. Interventions on microbiota are developed including prebiotics, probiotics, and fecal microbial transplantation (FMT). FMT via oral capsules also advances in recent with limited safety concerns compared with invasive routes. A hypothesis is thus raised that gut microbiome intervention via oral FMT can be a potential safe approach to encourage healthy aging, with multiple aspects evaluated for clinical phenotype of frailty, anthropometric measurement, cognitive function, cardiovascular aging, physical function, living activity, hippocampal volume, telomere length, cognitive biomarkers, inflammatory biomarkers, altered microbial composition and metabolites.

Detailed Description

Objective: To explore the effect, safety and underlying mechanisms of gut microbiome intervention via FMT on aging. Study Design: A multi-center, randomized, blinded, placebo-controlled pilot study. Data quality control and statistical analysis: The investigators have invited professional statistic analysts to assist analyzing data and a third party to supervise data quality. Ethics: The Ethics Committee of Fuwai Hospital approved this study. Informed consents before patient enrollment are required.

Study Timeline

• Status Verified: 2022-10
• Study First Submitted: 2022-10-20
• Study First Submitted QC: 2022-10-27
• Study First Posted: 2022-10-28
• Last Update Submitted: 2022-10-31
• Last Update Posted: 2022-11-02
• Study Start: 2023-01-01
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 210

Inclusion Criteria

1. Age 70-85 years.
2. Patients with informed consent after thorough explanation.

Exclusion Criteria

1. Participants of other clinical trials;
2. Antibiotics or probiotics usage within last 4 weeks;
3. Severe hepatic or renal diseases ((ALT >3 times the upper limit of normal value, or end stage renal disease on dialysis or eGFR <30 mL/min/1.73 m2, or serum creatinine >2.5 mg/dl [>221 μmol/L]);
4. History of large atherosclerotic cerebral infarction or hemorrhagic stroke (not including lacunar infarction and transient ischemic attack [TIA]);
5. Hospitalization for myocardial infarction within last 6 months; Coronary revascularization (PCI or CABG) within last 12 months; Planned for PCI or CABG in the next 6 months;
6. NYHA class III-IV heart failure; Hospitalization for chronic heart failure exacerbation within last 6 months;
7. Severe valvular diseases; Potential for surgery or percutaneous valve replacement within the study period;
8. Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Rheumatic heart disease; Congenital heart disease;
9. History of dementia, Parkinson's disease, intracranial infection, intracranial tumor, schizophrenia, anxiety, depression;
10. History of neurosurgical operation;
11. History of gastrointestinal tumor, gastrointestinal surgery, inflammatory bowel disease; Hospitalization for peptic ulcer disease exacerbation within last 6 months or anticipated hospitalization for peptic ulcer disease the next 6 months;
12. Hypertension with uncontrolled blood pressure ≥180/110mmHg;
13. Diabetes Mellitus with uncontrolled fasting glucose level ≥200mg/dl (11.1mmol/L), or HbA1C>8%;
14. Addicted to alcohol; Use of medication influencing cognitive function(i.e., antihistamine, antipsychotic);
15. General anesthesia within last 3 months;
16. Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome, life expectancy <1 year;
17. Impaired verbal communication who are incapable of providing their own informed consent, or incapable of self-care;
18. Special diet influencing microbiota (i.e. vegetarian);
19. Other conditions inappropriate for recruitment according to the investigators.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo capsules	Placebo capsules	Placebo capsules that do not contain donor stool or any active drug. Placebo capsules will be orally taken on week 0, week 4, week 8, week 12, week 24, week 36, week 48, week 60, week 72, week 84.
FMT capsules	FMT capsules	FMT capsules containing extensively screened donor stool. FMT capsules will be orally taken on week 0, week 4, week 8, week 12, week 24, week 36, week 48, week 60, week 72, week 84.

Primary Outcome Measures

Name	Time	Method
Proportion of participants with reduced frailty score at week 96 follow-up	week 96	Frailty score via CHS criteria of five frailty components, compared with baseline

Secondary Outcome Measures

Name	Time	Method
Change from baseline in Pulse wave velocity(PWV)	week 48, week 96	Change for Pulse wave velocity(PWV)
Change from baseline in Body Mass Index (BMI)	week 4, week 8, week 12, week 24, week 48, week 72, week 96	Change for Body Mass Index
Change from baseline in telomere length	week 48, week 96	Change from baseline in telomere length
Change from baseline in Cognitive assessment via Montreal Cognitive Assessment(MoCA)	week 24, week 48, week 72, week 96, compared with baseline	MoCA (Montreal Cognitive Assessment) ranging from 0 to 30, with lower score indicating worse outcome
Change from baseline in cognitive biomarkers	week 12, week 24, week 48, week 72, week 96	plasma levels of cognitive biomarkers for BDNF、tau、Aβ-40、Aβ42
Proportion of participants with reduced frailty score at week 12 follow-up	week 12	Frailty score via CHS criteria of five frailty components, compared with baseline
Proportion of participants with reduced frailty score at week 24 follow-up	week 24	Frailty score via CHS criteria of five frailty components, compared with baseline
Proportion of participants with reduced frailty score at week 72 follow-up	week 72	Frailty score via CHS criteria of five frailty components, compared with baseline
Change from baseline in Frailty score	week 12, week 24, week 48, week 72, week 96, compared with baseline	Frailty score via CHS criteria of five frailty components, ranging from 0 to 5, with higher score indicating worse outcome
Change from baseline in Hippocampal volumes	week 48, week 96	Hippocampal volumes evaluated by Magnet Resonance Imaging
Change from baseline in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis	week 12, week 24, week 48, week 72, week 96	Change in Intestinal Microbiota Composition Pre- and Post-intervention (FMT or Placebo) via Metagenomic Analysis, stratified by: 1. Randomisation; 2. Change in Office SBP
Change from baseline in Plasma Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis	week 12, week 24, week 48, week 72, week 96	Change in Plasma Metabolite Composition Pre-and Post-intervention (FMT or Placebo) via Metabolomic Analysis
Proportion of participants with reduced frailty score at week 48 follow-up	week 48	Frailty score via CHS criteria of five frailty components, compared with baseline
Change from baseline in Cognitive assessment via Mini Mental State Examination(MMSE)	week 24, week 48, week 72, week 96, compared with baseline	MMSE (Mini Mental State Examination) ranging from 0 to 30, with lower score indicating worse outcome
Change from baseline in office DBP	week 4, week 8, week 12, week 24, week 48, week 72, week 96	change for office diastolic blood pressure(DBP)
Change from baseline in inflammatory biomarkers	week 12, week 24, week 48, week 72, week 96	plasma levels of inflammatory biomarkers for hs-C-reactive protein (hs-CRP)、 interleukin 6(IL-6)、interleukin 1 β(IL-1 β) 、interleukin10 (IL-10)、tumor necrosis factor α(TNF-α)
Number of Participants with Adverse Events (AEs) as a Measure of Safety	week 12, week 24, week 48, week 72, week 96	Number of Participants with Adverse Events (AEs) as a Measure of Safety
Change from baseline in blood HbA1c level	week 12, week 24, week 48, week 96	Change for blood glycosylated hemoglobin, type A1C (HbA1c) level
Change from baseline in physical function assessment via 6MWT	week 12, week 24, week 48, week 72, week 96	6-minute walking test(6MWT)
Change from baseline in blood fasting glucose level	week 12, week 24, week 48, week 96	Change for blood fasting glucose level
Change from baseline in Intestinal Microbiota Function assessed by KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis	week 12, week 24, week 48, week 72, week 96	Change in Intestinal Microbiota Function assessed by KEGG Orthology (KO) Pre- and Post-intervention (FMT or Placebo) via Metagenomic Analysis, stratified by: 1. Randomisation; 2. Change in Office SBP
Change from baseline in Ankle-Brachial Blood Pressure Index(ABI)	week 48, week 96	Change for ABI as an objective measurement of arterial insufficiency based on the ratio of ankle systolic pressure to brachial systolic pressure.
Change from baseline in daily function assessment via Activity of Daily Living (ADL)	week 12, week 24, week 48, week 72, week 96	Activity of Daily Living (ADL) ranging from 0 to 100, with lower score indicating worse outcome
Change from baseline in office SBP	week 4, week 8, week 12, week 24, week 48, week 72, week 96	change for office systolic blood pressure(SBP)
Change from baseline in Blood Lipid Level	week 12, week 24, week 48, week 96	Change for Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)