Effect of Gut Microbiome Intervention on Aging Via Oral FMT (STEP-aging)

Effect of Fecal Microbiota Transplantation on Aging and the Underlying Mechanism of Gut Microbiome Restoration: a Randomized Clinical Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Frailty; Aging
• Intervention / Treatment: Biological: FMT capsules; Other: Placebo capsules

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 Type: Interventional
• Enrollment (Estimated): 210
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jun Cai, MD,PhD; Email: caijun7879@126.com
• Study Contact Backup: Name: Luyun Fan, MD,PhD; Phone Number: 01081992131; Email: katevan@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Chao-Yang Hospital, Capital Medical University
      • Contact: Yifan Fan, MD
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Hospital
      • Contact: Ni Zhang, MD
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Chinese People's Liberation Army (PLA) General Hospital
      • Contact: Guogang Xu, MD
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Xuanwu Hospital, Capital Medical University
      • Contact: Jing Li, MD
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Huadong Hospital Affiliated to Fudan University
      • Contact: Kailei Shi, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Hospital
      • Contact: Wei Yu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 66 years to 81 years (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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 28, week 32, week 36, week 48, week 52, week 56, week 60, week 72, week 76, week 80, week 84.	Biological: FMT capsules; FMT capsules containing extensively screened donor stool.
Placebo Comparator: 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 28, week 32, week 36, week 48, week 52, week 56, week 60, week 72, week 76, week 80, week 84.	Other: Placebo capsules; Placebo capsules that do not contain donor stool or any active drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with reduced frailty score at week 96 follow-up	Frailty score via CHS criteria of five frailty components, compared with baseline	week 96

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
• Investigators: Principal Investigator: Jun Cai, MD,PhD, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Chinese Institutes for Medical Research

Publications and helpful links

General Publications

• Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146.
• Ghosh TS, Rampelli S, Jeffery IB, Santoro A, Neto M, Capri M, Giampieri E, Jennings A, Candela M, Turroni S, Zoetendal EG, Hermes GDA, Elodie C, Meunier N, Brugere CM, Pujos-Guillot E, Berendsen AM, De Groot LCPGM, Feskins EJM, Kaluza J, Pietruszka B, Bielak MJ, Comte B, Maijo-Ferre M, Nicoletti C, De Vos WM, Fairweather-Tait S, Cassidy A, Brigidi P, Franceschi C, O'Toole PW. Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut. 2020 Jul;69(7):1218-1228. doi: 10.1136/gutjnl-2019-319654. Epub 2020 Feb 17.
• Ng TP, Feng L, Nyunt MS, Feng L, Niti M, Tan BY, Chan G, Khoo SA, Chan SM, Yap P, Yap KB. Nutritional, Physical, Cognitive, and Combination Interventions and Frailty Reversal Among Older Adults: A Randomized Controlled Trial. Am J Med. 2015 Nov;128(11):1225-1236.e1. doi: 10.1016/j.amjmed.2015.06.017. Epub 2015 Jul 6.
• Mullish BH, Quraishi MN, Segal JP, McCune VL, Baxter M, Marsden GL, Moore DJ, Colville A, Bhala N, Iqbal TH, Settle C, Kontkowski G, Hart AL, Hawkey PM, Goldenberg SD, Williams HRT. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut. 2018 Nov;67(11):1920-1941. doi: 10.1136/gutjnl-2018-316818. Epub 2018 Aug 28.
• Kundu P, Lee HU, Garcia-Perez I, Tay EXY, Kim H, Faylon LE, Martin KA, Purbojati R, Drautz-Moses DI, Ghosh S, Nicholson JK, Schuster S, Holmes E, Pettersson S. Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice. Sci Transl Med. 2019 Nov 13;11(518):eaau4760. doi: 10.1126/scitranslmed.aau4760.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: October 27, 2022
• First Posted (Actual): October 28, 2022

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Treatment; Microbiome; Fecal Microbiota Transplantation; Aging; Frailty
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Frailty; Therapeutics; Biological Therapy; Fecal Microbiota Transplantation
• Other Study ID Numbers: 2022-1784

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The collected data, study protocol, and SAP are planned to be shared after the study ends 3 years later (anticipated)
• IPD Sharing Time Frame: after the study ends 3 years later (anticipated)
• IPD Sharing Access Criteria: Access to these deidentified data will be required for written permission from the responsible investigation center and only for qualified researchers.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No