Effect of Gut Microbiome Restoration on Primary Hypertension Via FMT

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Fecal Microbiota Transplantation on Primary Hypertension and the Underlying Mechanism of Gut Microbiome Restoration: a Randomized Clinical Trial

Conditions
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Hypertension

Intervention / Treatment
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* Biological: FMT capsules
* Other: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 60 years. 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. Patients with informed consent after thorough explanation. Exclusion Criteria: Antibiotics or probiotics usage within last 4 weeks Participants of other clinical trials related to hypertension currently or within last 3 months Antihypertensive medications usage currently or within last month Diagnosed secondary hypertension 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 12 months. Sustained atrial fibrillation or arrhythmias at recruitment disturbing the electronic BP measurement. 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. Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome. Cognitive impairment or severe neuropsychiatric comorbidities who are incapable of providing their own informed consent. Participants preparing for or under pregnancy and/or lactation. Other conditions inappropriate for recruitment according to the investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMT capsules<br>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). | Biological: FMT capsules<br>* Intervention: FMT capsules containing extensively screened donor stool.<br>|
| Placebo Comparator: Placebo capsules<br>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). | Other: Placebo capsules<br>* Intervention: Placebo capsules that do not contain donor stool or any active drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change for Office Systolic Blood Pressure (SBP) | Change for Office Systolic Blood Pressure (SBP) | From baseline to Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change for Office SBP | Change for Office SDBP | Baseline, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Change for Office Diastolic Blood Pressure (DBP) | Change for Office Diastolic Blood Pressure (DBP) | Baseline, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Change for Home Systolic Blood Pressure (SBP) | Change for Home Systolic Blood Pressure (SBP) | Baseline, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Change for Home Diastolic Blood Pressure (DBP) | Change for Home Diastolic Blood Pressure (DBP) | Baseline, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Change for average SBP via 24-hour Ambulatory BP Monitoring | Change for average SBP via 24-hour Ambulatory BP Monitoring | Baseline, Day 30, Day 90 | 
| Change for average DBP via 24-hour Ambulatory BP Monitoring | Change for average DBP via 24-hour Ambulatory BP Monitoring | Baseline, Day 30, Day 90 | 
| Change for daytime average SBP via 24-hour Ambulatory BP Monitoring | Change for daytime average SBP via 24-hour Ambulatory BP Monitoring | Baseline, Day 30, Day 90 | 
| Change for daytime average DBP via 24-hour Ambulatory BP Monitoring | Change for daytime average DBP via 24-hour Ambulatory BP Monitoring | Baseline, Day 30, Day 90 | 
| Change for nightime average SBP via 24-hour Ambulatory BP Monitoring | Change for nightime average SBP via 24-hour Ambulatory BP Monitoring | Baseline, Day 30, Day 90 | 
| Change for nightime average DBP via 24-hour Ambulatory BP Monitoring | Change for nightime average DBP via 24-hour Ambulatory BP Monitoring | Baseline, Day 30, Day 90 | 
| Change for 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. | Baseline, Day 90 | 
| Number of Participants with Adverse Events (AEs) as a Measure of Safety | Number of Participants with Adverse Events (AEs) as a Measure of Safety | All AEs over 3 months | 
| Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis | Changes in Intestinal Microbiota Composition Pre- and Post-intervention (FMT or Placebo) via Metagenomic Analysis, stratified by: Randomisation Change in Office SBP | Baseline, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Changes in Intestinal Microbiota Function Pre- and Post-intervention via Metagenomic Analysis | Changes in Intestinal Microbiota Function Pre- and Post-intervention (FMT or Placebo) via Metagenomic Analysis, stratified by: Randomisation Change in Office SBP | Baseline, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Durability of Engraftment of Donor Microbiome Following FMT | Durability of engraftment of donor microbiome following FMT, measured by similarity comparison of intestinal microbiota composition between donor and recipient | Baseline, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Changes in Intestinal Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis | Changes in Intestinal Metabolite Composition Pre- and Post-intervention (FMT or Placebo) via Metabolomic Analysis, stratified by: Randomisation Change in Office SBP | Baseline, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Changes in Serum Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis | Changes in Serum Metabolite Composition Pre- and Post-intervention (FMT or Placebo) via Metabolomic Analysis, stratified by: Randomisation Change in Office SBP | Baseline, Day 7, Day 14, Day 30, Day 60, Day 90 | 
| Change for Fasting Blood Glucose Level | Change for Fasting Blood Glucose Level | Baseline, Day 90 | 
| Change for Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol) | Change for Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol) | Baseline, Day 90 | 
| Change for Body Mass Index | Change for Body Mass Index | Baseline, Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Microbiome, Treatment, Fecal Microbiota Transplantation