Effect of Intensive FMT on Primary Hypertension

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 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
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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, 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was observed after short-course FMT intervention but recovery after intervention termination(Trials. 2022;23(1):178, unpublished results).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.

Official Title
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Effect and Safety of Intensive Fecal Microbiota Transplantation on Primary Hypertension: 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 65 years. 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 the2010 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: 65 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 |
| --- | --- |
| Active Comparator: FMT capsules<br>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. | Biological: FMT capsules<br>* FMT capsules containing extensively screened donor stool.<br>|
| Placebo Comparator: Placebo capsules<br>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. | Other: Placebo capsules<br>* 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 in Office Systolic Blood Pressure (SBP) | Change in Office Systolic Blood Pressure (SBP) | From baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Office Systolic Blood Pressure (SBP) | Change in Office Systolic Blood Pressure (SBP) | Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 12 | 
| Change in Office Diastolic Blood Pressure (DBP) | Change in Office Diastolic Blood Pressure (DBP) | Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12 | 
| Change in Home Systolic Blood Pressure (SBP) | Change in Home Systolic Blood Pressure (SBP) | Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12 | 
| Change in Home Diastolic Blood Pressure (DBP) | Change in Home Diastolic Blood Pressure (DBP), compared with baseline | Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12 | 
| Change in average SBP via 24-hour Ambulatory BP Monitoring | Change in average SBP via 24-hour Ambulatory BP Monitoring | Baseline, Week 4, Week 8, Week 12 | 
| Change in average DBP via 24-hour Ambulatory BP Monitoring | Change in average DBP via 24-hour Ambulatory BP Monitoring | Baseline, Week 4, Week 8, Week 12 | 
| Change in daytime SBP via 24-hour Ambulatory BP Monitoring | Change in daytime SBP via 24-hour Ambulatory BP Monitoring | Baseline, Week 4, Week 8, Week 12 | 
| Change in daytime DBP via 24-hour Ambulatory BP Monitoring | Change in daytime DBP via 24-hour Ambulatory BP Monitoring | Baseline, Week 4, Week 8, Week 12 | 
| Change in nighttime SBP via 24-hour Ambulatory BP Monitoring | Change in nighttime SBP via 24-hour Ambulatory BP Monitoring | Baseline, Week 4, Week 8, Week 12 | 
| Change in nighttime DBP via 24-hour Ambulatory BP Monitoring | Change in nighttime DBP via 24-hour Ambulatory BP Monitoring | Baseline, Week 4, Week 8, Week 12 | 
| 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 12 weeks | 
| 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, Week 4, Week 8, Week 12 | 
| Changes in Intestinal Microbiota function revealed by KEGG pathways and KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis | Changes in Intestinal Microbiota function revealed by KEGG pathways and KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis, stratified by: Randomisation Change in Office SBP | Baseline, Week 4, Week 8, Week 12 | 
| 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, Week 4, Week 8, Week 12 | 
| Changes in Plasma Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis | Changes in Plasma Metabolite Composition Pre- and Post-intervention (FMT or Placebo) via Metabolomic Analysis, stratified by: Randomisation Change in Office SBP | Baseline, Week 4, Week 8, Week 12 | 
| Change in Fasting Blood Glucose Level | Change in Fasting Blood Glucose Level | Baseline, Week 4, Week 8, Week 12 | 
| Change in blood HbA1c level | Change in blood glycosylated hemoglobin, type A1C (HbA1c) level | Baseline, Week 4, Week 8, Week 12 | 
| Change in blood lipid level | Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol) | Baseline, Week 4, Week 8, Week 12 | 
| Change in Body Mass Index | Change in Body Mass Index | Baseline, Week 4, Week 8, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension, microbiome, fecal microbiota transplantation, treatment