Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FMT capsules | Experimental | 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. |
|
| Placebo capsules | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FMT capsules | Biological | FMT capsules containing extensively screened donor stool. |
| |
| 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 |
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Luyun Fan, MD,PhD | Contact | 01081992131 | katevan@163.com | |
| Jun Cai, MD,PhD | Contact | caijun7879@126.com |
| Name | Affiliation | Role |
|---|---|---|
| Jun Cai, MD,PhD | Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Chinese Institutes for Medical Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Chao-yang Hospital, Capital Medical University | Recruiting | Beijing | Beijing Municipality | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11253156 | Result | 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. | |
| 32066625 | Result |
Not provided
Not provided
The collected data, study protocol, and SAP are planned to be shared after the study ends 3 years later (anticipated)
after the study ends 3 years later (anticipated)
Access to these deidentified data will be required for written permission from the responsible investigation center and only for qualified researchers.
Not provided
Not provided
| ID | Term |
|---|---|
| D000073496 | Frailty |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo capsules |
| Other |
Placebo capsules that do not contain donor stool or any active drug. |
|
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:
| 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:
| 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 |
| Beijing Hospital | Recruiting | Beijing | Beijing Municipality | China |
|
| Chinese People's Liberation Army (PLA) General Hospital | Recruiting | Beijing | Beijing Municipality | China |
|
| Xuanwu Hospital, Capital Medical University | Recruiting | Beijing | Beijing Municipality | China |
|
| Huadong Hospital Affiliated to Fudan University | Recruiting | Shanghai | Shanghai Municipality | China |
|
| Zhejiang Hospital | Recruiting | Hangzhou | Zhejiang | China |
|
| 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. |
| 26159634 | Result | 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. |
| 30154172 | Result | 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. |
| 31723038 | Result | 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. |