Effect of Gut Microbiome Restoration on Primary Hypertension Via FMT

NCT ID: NCT04406129

Last Updated: 2021-07-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-17
• Study Completion Date: 2022-09-01

Brief Summary

Mounting preclinical and clinical evidences have proved the causal role of gut microbiota on the pathogenesis of primary hypertension. Restoration of gut microbiota ameliorated high BP in rodents and/or human cases.A hypothesis is thus raised that gut microbiome restoration can be a potential approach to ameliorate hypertension. This pilot study will utilize fecal microbiota transplantation (FMT) capsules, in comparison with placebo capsules, to investigate the effect, safety and underlying mechanisms of gut microbiome restoration on primary hypertension.

Detailed Description

Primary hypertension is a most prevalent cardiovascular diseases, and becomes a severe global public health issue because of the high morbidity and potential risk to other cardiovascular diseases. Several animal studies and diverse patient cohorts reported that the disorder of gut microbiome correlated with hypertension. Based on the investigators' previous work findings of metagenomics analysis, fecal transplantation and metabolomics changes in hypertension and pre-hypertension patients, a casual role of gut microbiome disorder was observed in primary hypertension and raised a hypothesis that gut microbiome restoration can be a potential approach to ameliorate hypertension. Recent studies indicated FMT, prebiotics, probiotics, dietary changes and other methodologies can assist gut microbiome restoration in diseases such as type 2 diabetes. The investigators therefore develop two pilot studies respectively utilizing FMT capsules (Pilot Study I) and innovative dietary changes (Pilot Study II) to explore the effect, safety and underlying mechanisms of gut microbiome restoration on hypertension. These pilot studies also present as the clinical translational section of the research project "The Role of Gut Microbiome in the Pathogenesis of Essential Hypertension"(Project ID 81630014, sponsored by National Natural Science Foundation of China).

This study is the Study I:

Objective: To explore the effect, safety and underlying mechanisms of gut microbiome restoration via FMT on primary hypertension.

Study Design: A multicenter, randomized, double-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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

FMT capsules

Intervention: FMT capsules containing extensively screened donor stool. FMT capsules will be orally taken on Day 1, Day 7 (Week 1) and Day 14 (Week 2).

Group Type: EXPERIMENTAL

FMT capsules

Intervention Type: BIOLOGICAL

Intervention: FMT capsules containing extensively screened donor stool.

Placebo capsules

Intervention: Placebo capsules that do not contain donor stool or any active drug. Placebo capsules will be orally taken on Day 1, Day 7 (Week 1) and Day 14 (Week 2).

Group Type: PLACEBO_COMPARATOR

Placebo capsules

Intervention Type: OTHER

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

Interventions

FMT capsules

Intervention: FMT capsules containing extensively screened donor stool.

Intervention Type: BIOLOGICAL

Placebo capsules

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age 18~60 years.

2. Established Diagnosis of Grade 1 Hypertension (initial diagnosis or free from antihypertensive drugs within a month): 140mmHg≤ Office SBP<160mmHg for three measurements at different days without any antihypertensive medications, according to the "2010 Chinese Guidelines for Prevention and Treatment of Hypertension".

3. Patients with informed consent after thorough explanation.

Exclusion Criteria

1. Antibiotics or probiotics usage within last 4 weeks

2. Participants of other clinical trials related to hypertension currently or within last 3 months

3. Antihypertensive medications usage currently or within last month

4. Diagnosed secondary hypertension

5. 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])

6. History of large atherosclerotic cerebral infarction or hemorrhagic stroke (not including lacunar infarction and transient ischemic attack [TIA])

7. 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 12 months.

8. Sustained atrial fibrillation or arrhythmias at recruitment disturbing the electronic BP measurement.

9. NYHA class III-IV heart failure; Hospitalization for chronic heart failure exacerbation within last 6 months.

10. Severe valvular diseases; Potential for surgery or percutaneous valve replacement within the study period.

11. Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Rheumatic heart disease; Congenital heart disease.

12. Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome.

13. Cognitive impairment or severe neuropsychiatric comorbidities who are incapable of providing their own informed consent.

14. Participants preparing for or under pregnancy and/or lactation.

15. Other conditions inappropriate for recruitment according to the investigators.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Natural Science Foundation of China

OTHER_GOV

Sponsor Role: collaborator

Chinese Academy of Medical Sciences, Fuwai Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jun Cai

Professor, Director of Hypertension Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Cai, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Sciences, Fuwai Hospital

Locations

Fuwai Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status: NOT_YET_RECRUITING

The Second Affiliated Hospital of Shantou University

Shantou, Guangdong, China

Site Status: RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, China

Site Status: RECRUITING

Shanxi Bethune Hospital

Taiyuan, Shanxi, China

Site Status: RECRUITING

Southern University of Science and Technology Hospital

Shenzhen, Shenzhen, China

Site Status: RECRUITING

The People's Hospital of Ji Xian District

Tianjin, Tianjin Municipality, China

Site Status: NOT_YET_RECRUITING

Fuwai Yunnan Cardiovascular Hospital

Kunming, Yunnan, China

Site Status: RECRUITING

Countries

China

Central Contacts

LUYUN FAN

Role: CONTACT

fuwai_fanluyun@163.com

01088392165

LU WANG

Role: CONTACT

wanglu@fuwai.com

01088392165

Facility Contacts

Jun Cai

Role: primary

Youren Chen

Role: primary

Peili Bu

Role: primary

Jie Ren

Role: primary

Bingpo Zhu

Role: primary

Jinfeng Yang

Role: primary

Zihong Guo

Role: primary

References

Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, Wu S, Liu W, Cui Q, Geng B, Zhang W, Weldon R, Auguste K, Yang L, Liu X, Chen L, Yang X, Zhu B, Cai J. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017 Feb 1;5(1):14. doi: 10.1186/s40168-016-0222-x.

Reference Type: BACKGROUND

PMID: 28143587 (View on PubMed)

Cammarota G, Ianiro G, Tilg H, Rajilic-Stojanovic M, Kump P, Satokari R, Sokol H, Arkkila P, Pintus C, Hart A, Segal J, Aloi M, Masucci L, Molinaro A, Scaldaferri F, Gasbarrini G, Lopez-Sanroman A, Link A, de Groot P, de Vos WM, Hogenauer C, Malfertheiner P, Mattila E, Milosavljevic T, Nieuwdorp M, Sanguinetti M, Simren M, Gasbarrini A; European FMT Working Group. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017 Apr;66(4):569-580. doi: 10.1136/gutjnl-2016-313017. Epub 2017 Jan 13.

Reference Type: BACKGROUND

PMID: 28087657 (View on PubMed)

Translating Microbiome Research into Therapies: The Path Ahead. Cell. 2020 Apr 2;181(1):20-21. doi: 10.1016/j.cell.2020.03.009. No abstract available.

Reference Type: BACKGROUND

PMID: 32243790 (View on PubMed)

Fan L, Chen J, Zhang Q, Ren J, Chen Y, Yang J, Wang L, Guo Z, Bu P, Zhu B, Zhao Y, Wang Y, Liu X, Wang W, Chen Z, Gao Q, Zheng L, Cai J. Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial. Microbiome. 2025 May 23;13(1):133. doi: 10.1186/s40168-025-02118-6.

Reference Type: DERIVED

PMID: 40410854 (View on PubMed)

Fan L, Ren J, Chen Y, Wang Y, Guo Z, Bu P, Yang J, Ma W, Zhu B, Zhao Y, Cai J. Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study. Trials. 2022 Feb 24;23(1):178. doi: 10.1186/s13063-022-06086-2.

Reference Type: DERIVED

PMID: 35209934 (View on PubMed)

Other Identifiers

2017-GZ10 (Part I)

Identifier Type: -

Identifier Source: org_study_id