Clinical trial NCT05598112: Effect of Gut Microbiome Intervention on Aging Via Oral FMT
Official title: Effect of Fecal Microbiota Transplantation on Aging and the Underlying Mechanism of Gut Microbiome Restoration: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Aging
Frailty
Keywords: Aging
Frailty
Microbiome
Treatment
Fecal Microbiota Transplantation
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
First posted: 2022-10-28
Enrollment: 210
Sex: ALL
Minimum age (years): 70
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants with reduced frailty score at week 96 follow-up
timeFrame: week 96
Secondary outcomes:
measure: Proportion of participants with reduced frailty score at week 12 follow-up
timeFrame: week 12
measure: Proportion of participants with reduced frailty score at week 24 follow-up
timeFrame: week 24
measure: Proportion of participants with reduced frailty score at week 48 follow-up
timeFrame: week 48
measure: Proportion of participants with reduced frailty score at week 72 follow-up
timeFrame: week 72
measure: Change from baseline in Frailty score
timeFrame: week 12, week 24, week 48, week 72, week 96, compared with baseline
measure: Change from baseline in telomere length
timeFrame: week 48, week 96
measure: Change from baseline in Cognitive assessment via Mini Mental State Examination(MMSE)
timeFrame: week 24, week 48, week 72, week 96, compared with baseline
measure: Change from baseline in Cognitive assessment via Montreal Cognitive Assessment(MoCA)
timeFrame: week 24, week 48, week 72, week 96, compared with baseline
measure: Change from baseline in Hippocampal volumes
timeFrame: week 48, week 96
measure: Change from baseline in cognitive biomarkers
timeFrame: week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in inflammatory biomarkers
timeFrame: week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis
timeFrame: week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in Intestinal Microbiota Function assessed by KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis
timeFrame: week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in Plasma Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
timeFrame: week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in Ankle-Brachial Blood Pressure Index(ABI)
timeFrame: week 48, week 96
measure: Change from baseline in Pulse wave velocity(PWV)
timeFrame: week 48, week 96
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety
timeFrame: week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in Body Mass Index (BMI)
timeFrame: week 4, week 8, week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in office SBP
timeFrame: week 4, week 8, week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in office DBP
timeFrame: week 4, week 8, week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in Blood Lipid Level
timeFrame: week 12, week 24, week 48, week 96
measure: Change from baseline in blood fasting glucose level
timeFrame: week 12, week 24, week 48, week 96
measure: Change from baseline in blood HbA1c level
timeFrame: week 12, week 24, week 48, week 96
measure: Change from baseline in physical function assessment via 6MWT
timeFrame: week 12, week 24, week 48, week 72, week 96
measure: Change from baseline in daily function assessment via Activity of Daily Living (ADL)
timeFrame: week 12, week 24, week 48, week 72, week 96
Other outcomes:
Locations:
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Jun Cai, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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