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

Primary Purpose

Aging, Frailty

Status

Not yet recruiting

Phase

Early Phase 1

Locations

Study Type

Interventional

Intervention

FMT capsules

Placebo capsules

About this trial

This is an interventional treatment trial for Aging focused on measuring Aging, Frailty, Microbiome, Treatment, Fecal Microbiota Transplantation

Eligibility Criteria

70 Years - 85 Years (Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Participants of other clinical trials;
Antibiotics or probiotics usage within last 4 weeks;
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]);
History of large atherosclerotic cerebral infarction or hemorrhagic stroke (not including lacunar infarction and transient ischemic attack [TIA]);
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;
NYHA class III-IV heart failure; Hospitalization for chronic heart failure exacerbation within last 6 months;
Severe valvular diseases; Potential for surgery or percutaneous valve replacement within the study period;
Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Rheumatic heart disease; Congenital heart disease;
History of dementia, Parkinson's disease, intracranial infection, intracranial tumor, schizophrenia, anxiety, depression;
History of neurosurgical operation;
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;
Hypertension with uncontrolled blood pressure ≥180/110mmHg;
Diabetes Mellitus with uncontrolled fasting glucose level ≥200mg/dl (11.1mmol/L), or HbA1C>8%;
Addicted to alcohol; Use of medication influencing cognitive function(i.e., antihistamine, antipsychotic);
General anesthesia within last 3 months;
Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome, life expectancy <1 year;
Impaired verbal communication who are incapable of providing their own informed consent, or incapable of self-care;
Special diet influencing microbiota (i.e. vegetarian);
Other conditions inappropriate for recruitment according to the investigators.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

FMT capsules

Placebo capsules

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Proportion of participants with reduced frailty score at week 96 follow-up

Frailty score via CHS criteria of five frailty components, compared with baseline

Secondary Outcome Measures

Proportion of participants with reduced frailty score at week 12 follow-up

Frailty score via CHS criteria of five frailty components, compared with baseline

Proportion of participants with reduced frailty score at week 24 follow-up

Frailty score via CHS criteria of five frailty components, compared with baseline

Proportion of participants with reduced frailty score at week 48 follow-up

Frailty score via CHS criteria of five frailty components, compared with baseline

Proportion of participants with reduced frailty score at week 72 follow-up

Frailty score via CHS criteria of five frailty components, compared with baseline

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

Change from baseline in telomere length

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

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

Change from baseline in Hippocampal volumes

Hippocampal volumes evaluated by Magnet Resonance Imaging

Change from baseline in cognitive biomarkers

plasma levels of cognitive biomarkers for BDNF、tau、Aβ-40、Aβ42

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)

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

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

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

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.

Change from baseline in Pulse wave velocity(PWV)

Change for Pulse wave velocity(PWV)

Number of Participants with Adverse Events (AEs) as a Measure of Safety

Change from baseline in Body Mass Index (BMI)

Change for Body Mass Index

Change from baseline in office SBP

change for office systolic blood pressure(SBP)

Change from baseline in office DBP

change for office diastolic blood pressure(DBP)

Change from baseline in Blood Lipid Level

Change for Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)

Change from baseline in blood fasting glucose level

Change for blood fasting glucose level

Change from baseline in blood HbA1c level

Change for blood glycosylated hemoglobin, type A1C (HbA1c) level

Change from baseline in physical function assessment via 6MWT

6-minute walking test(6MWT)

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

Full Information

NCT ID

NCT05598112

First Posted

October 20, 2022

Last Updated

October 31, 2022

Sponsor

Chinese Academy of Medical Sciences, Fuwai Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05598112

Brief Title

Effect of Gut Microbiome Intervention on Aging Via Oral FMT

Acronym

STEP-aging

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 1, 2023 (Anticipated)

Primary Completion Date

December 31, 2026 (Anticipated)

Study Completion Date

December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese Academy of Medical Sciences, Fuwai Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aging, Frailty

Keywords

Aging, Frailty, Microbiome, Treatment, Fecal Microbiota Transplantation

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

210 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

FMT capsules

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo capsules

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

FMT capsules

Intervention Description

FMT capsules containing extensively screened donor stool.

Intervention Type

Other

Intervention Name(s)

Placebo capsules

Intervention Description

Placebo capsules that do not contain donor stool or any active drug.

Primary Outcome Measure Information:

Title

Proportion of participants with reduced frailty score at week 96 follow-up

Description

Frailty score via CHS criteria of five frailty components, compared with baseline

Time Frame

week 96

Secondary Outcome Measure Information:

Title

Proportion of participants with reduced frailty score at week 12 follow-up

Description

Frailty score via CHS criteria of five frailty components, compared with baseline

Time Frame

week 12

Title

Proportion of participants with reduced frailty score at week 24 follow-up

Description

Frailty score via CHS criteria of five frailty components, compared with baseline

Time Frame

week 24

Title

Proportion of participants with reduced frailty score at week 48 follow-up

Description

Frailty score via CHS criteria of five frailty components, compared with baseline

Time Frame

week 48

Title

Proportion of participants with reduced frailty score at week 72 follow-up

Description

Frailty score via CHS criteria of five frailty components, compared with baseline

Time Frame

week 72

Title

Change from baseline in Frailty score

Description

Frailty score via CHS criteria of five frailty components, ranging from 0 to 5, with higher score indicating worse outcome

Time Frame

week 12, week 24, week 48, week 72, week 96, compared with baseline

Title

Change from baseline in telomere length

Description

Change from baseline in telomere length

Time Frame

week 48, week 96

Title

Change from baseline in Cognitive assessment via Mini Mental State Examination(MMSE)

Description

MMSE (Mini Mental State Examination) ranging from 0 to 30, with lower score indicating worse outcome

Time Frame

week 24, week 48, week 72, week 96, compared with baseline

Title

Change from baseline in Cognitive assessment via Montreal Cognitive Assessment(MoCA)

Description

MoCA (Montreal Cognitive Assessment) ranging from 0 to 30, with lower score indicating worse outcome

Time Frame

week 24, week 48, week 72, week 96, compared with baseline

Title

Change from baseline in Hippocampal volumes

Description

Hippocampal volumes evaluated by Magnet Resonance Imaging

Time Frame

week 48, week 96

Title

Change from baseline in cognitive biomarkers

Description

plasma levels of cognitive biomarkers for BDNF、tau、Aβ-40、Aβ42

Time Frame

week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in inflammatory biomarkers

Description

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)

Time Frame

week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis

Description

Change in Intestinal Microbiota Composition Pre- and Post-intervention (FMT or Placebo) via Metagenomic Analysis, stratified by: Randomisation Change in Office SBP

Time Frame

week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in Intestinal Microbiota Function assessed by KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis

Description

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

Time Frame

week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in Plasma Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis

Description

Change in Plasma Metabolite Composition Pre-and Post-intervention (FMT or Placebo) via Metabolomic Analysis

Time Frame

week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in Ankle-Brachial Blood Pressure Index(ABI)

Description

Change for ABI as an objective measurement of arterial insufficiency based on the ratio of ankle systolic pressure to brachial systolic pressure.

Time Frame

week 48, week 96

Title

Change from baseline in Pulse wave velocity(PWV)

Description

Change for Pulse wave velocity(PWV)

Time Frame

week 48, week 96

Title

Number of Participants with Adverse Events (AEs) as a Measure of Safety

Description

Number of Participants with Adverse Events (AEs) as a Measure of Safety

Time Frame

week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in Body Mass Index (BMI)

Description

Change for Body Mass Index

Time Frame

week 4, week 8, week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in office SBP

Description

change for office systolic blood pressure(SBP)

Time Frame

week 4, week 8, week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in office DBP

Description

change for office diastolic blood pressure(DBP)

Time Frame

week 4, week 8, week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in Blood Lipid Level

Description

Change for Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)

Time Frame

week 12, week 24, week 48, week 96

Title

Change from baseline in blood fasting glucose level

Description

Change for blood fasting glucose level

Time Frame

week 12, week 24, week 48, week 96

Title

Change from baseline in blood HbA1c level

Description

Change for blood glycosylated hemoglobin, type A1C (HbA1c) level

Time Frame

week 12, week 24, week 48, week 96

Title

Change from baseline in physical function assessment via 6MWT

Description

6-minute walking test(6MWT)

Time Frame

week 12, week 24, week 48, week 72, week 96

Title

Change from baseline in daily function assessment via Activity of Daily Living (ADL)

Description

Activity of Daily Living (ADL) ranging from 0 to 100, with lower score indicating worse outcome

Time Frame

week 12, week 24, week 48, week 72, week 96

10. Eligibility

Sex

All

Minimum Age & Unit of Time

70 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 70-85 years. Patients with informed consent after thorough explanation. Exclusion Criteria: Participants of other clinical trials; Antibiotics or probiotics usage within last 4 weeks; 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]); History of large atherosclerotic cerebral infarction or hemorrhagic stroke (not including lacunar infarction and transient ischemic attack [TIA]); 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; NYHA class III-IV heart failure; Hospitalization for chronic heart failure exacerbation within last 6 months; Severe valvular diseases; Potential for surgery or percutaneous valve replacement within the study period; Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Rheumatic heart disease; Congenital heart disease; History of dementia, Parkinson's disease, intracranial infection, intracranial tumor, schizophrenia, anxiety, depression; History of neurosurgical operation; 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; Hypertension with uncontrolled blood pressure ≥180/110mmHg; Diabetes Mellitus with uncontrolled fasting glucose level ≥200mg/dl (11.1mmol/L), or HbA1C>8%; Addicted to alcohol; Use of medication influencing cognitive function(i.e., antihistamine, antipsychotic); General anesthesia within last 3 months; Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome, life expectancy <1 year; Impaired verbal communication who are incapable of providing their own informed consent, or incapable of self-care; Special diet influencing microbiota (i.e. vegetarian); Other conditions inappropriate for recruitment according to the investigators.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Luyun Fan, MD,PhD

Phone

01088392165

fuwai_fanluyun@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Jun Cai, MD,PhD

caijun7879@126.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jun Cai, MD,PhD

Organizational Affiliation

Fuwai Hospital, CAMS & PUMC

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Citations:

PubMed Identifier

11253156

Citation

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.

Results Reference

result

PubMed Identifier

32066625

Citation

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.

Results Reference

result

PubMed Identifier

26159634

Citation

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.

Results Reference

result

PubMed Identifier

30154172

Citation

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.

Results Reference

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PubMed Identifier

31723038

Citation

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.

Results Reference

result

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Effect of Gut Microbiome Intervention on Aging Via Oral FMT

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