Hypertension
Conditions
Keywords
hypertension, microbiome, fecal microbiota transplantation, treatment
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was observed after short-course FMT intervention but recovery after intervention termination(Trials. 2022;23(1):178, unpublished results).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.
Interventions
BIOLOGICALFMT capsules
FMT capsules containing extensively screened donor stool.
OTHERPlacebo capsules
Placebo capsules that do not contain donor stool or any active drug.
Sponsors
Chinese Academy of Medical Sciences, Fuwai Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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 the2010 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Office Systolic Blood Pressure (SBP) | From baseline to Week 8 | Change in Office Systolic Blood Pressure (SBP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 Office Diastolic Blood Pressure (DBP) |
| 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 Systolic Blood Pressure (SBP) |
| Change in Home 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 Diastolic Blood Pressure (DBP), compared with baseline |
| Change in average SBP via 24-hour Ambulatory BP Monitoring | Baseline, Week 4, Week 8, Week 12 | Change in average SBP 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 average DBP 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 SBP 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 daytime DBP 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 SBP via 24-hour Ambulatory BP Monitoring |
| Change in nighttime DBP 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 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 Systolic Blood Pressure (SBP) |
| Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis | Baseline, Week 4, Week 8, Week 12 | Changes in Intestinal Microbiota Composition Pre- and Post-intervention (FMT or Placebo) via Metagenomic Analysis, stratified by: 1. Randomisation 2. Change in Office SBP |
| Changes in Intestinal Microbiota function revealed by KEGG pathways and KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis | 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, stratified by: 1. Randomisation 2. Change in Office SBP |
| Durability of Engraftment of Donor Microbiome Following FMT | Baseline, Week 4, Week 8, Week 12 | Durability of engraftment of donor microbiome following FMT, measured by similarity comparison of intestinal microbiota composition between donor and recipient |
| Changes in Plasma Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis | Baseline, Week 4, Week 8, Week 12 | Changes in Plasma Metabolite Composition Pre- and Post-intervention (FMT or Placebo) via Metabolomic Analysis, stratified by: 1. Randomisation 2. Change in Office SBP |
| Change in Fasting Blood Glucose Level | Baseline, Week 4, Week 8, Week 12 | Change in Fasting Blood Glucose Level |
| Change in blood HbA1c level | Baseline, Week 4, Week 8, Week 12 | Change in blood glycosylated hemoglobin, type A1C (HbA1c) level |
| Change in blood lipid level | Baseline, Week 4, Week 8, Week 12 | Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol) |
| Change in Body Mass Index | Baseline, Week 4, Week 8, Week 12 | Change in Body Mass Index |
| Number of Participants with Adverse Events (AEs) as a Measure of Safety | All AEs over 12 weeks | Number of Participants with Adverse Events (AEs) as a Measure of Safety |
Countries
China
Contacts
Primary ContactJun Jun, MD,PhD
Backup ContactJun Jun, MD,PhD
Outcome results
None listed