Effect of Intensive FMT on Primary Hypertension

NCT ID: NCT05608447

Last Updated: 2022-11-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2023-09-30

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 study will perform intense fecal microbiota transplantation (FMT) intervention via oral capsules, in comparison with placebo capsules, to investigate the effect, safety and underlying mechanisms of gut microbiome intervention 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, a casual role of gut microbiome disorder was observed in primary hypertension (Microbiome. 2017;5(1):14.), and trend of ameliorating SBP was observed after short-course FMT intervention but recovery after intervention termination(Trials. 2022;23(1):178, unpublished results). The investigators therefore developed a consecutive study of intensive FMT intervention on primary hypertension.

Objective: To explore the effect, safety and underlying mechanisms of intensive FMT on primary hypertension.

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.

Conditions

Hypertension

Study Design

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

Study Groups

FMT capsules

FMT capsules containing extensively screened donor stool. FMT capsules will be orally taken on Day 0 (randomization), Day 1, Day 2, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49.

Group Type: ACTIVE_COMPARATOR

FMT capsules

Intervention Type: BIOLOGICAL

FMT capsules containing extensively screened donor stool.

Placebo capsules

Placebo capsules that do not contain donor stool or any active drug. Placebo capsules will be orally taken on Day 0 (randomization), Day 1, Day 2, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49.

Group Type: PLACEBO_COMPARATOR

Placebo capsules

Intervention Type: OTHER

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

Interventions

FMT capsules

FMT capsules containing extensively screened donor stool.

Intervention Type: BIOLOGICAL

Placebo capsules

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age 18~65 years.

2. Established Diagnosis of Grade 1 Hypertension (initial diagnosis or free from antihypertensive drugs within a month): 140mmHg≤ Office SBP<160mmHg and/or 90mmHg≤ Office DBP<100mmHg 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: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences, Fuwai Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jun Cai

Professor, Doctoral supervisor, Assistant Principal of Fuwai Hospital, Chief of Hypertension Center, Fuwai Hospital,PUMC&CAMS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Cai, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Sciences, Fuwai Hospital

Locations

The Second Affiliated Hospital of Shantou University

Shantou, Guangdong, China

Shanxi Bethune Hospital

Taiyuan, Shanxi, China

The People's Hospital of Ji Xian District

Tianjin, Tianjin Municipality, China

Countries

China

Central Contacts

Jun Jun, MD,PhD

Role: CONTACT

caijun7879@126.com

86-010-88392165

Jun Jun, MD,PhD

Role: CONTACT

caijun7879@126.com

86-010-60866432

Facility Contacts

Youren Chen

Role: primary

Jie Ren

Role: primary

Jinfeng Yang

Role: primary

References

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)

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: RESULT

PMID: 28143587 (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: RESULT

PMID: 35209934 (View on PubMed)

Other Identifiers

2017-GZ10 (Part III)

Identifier Type: -

Identifier Source: org_study_id