Clinical trial NCT04406129: Effect of Gut Microbiome Restoration on Primary Hypertension Via FMT
Official title: Effect of Fecal Microbiota Transplantation on Primary Hypertension and the Underlying Mechanism of Gut Microbiome Restoration: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Hypertension
Keywords: Hypertension
Microbiome
Treatment
Fecal Microbiota Transplantation
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2020-05-28
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: 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 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.

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.

Primary outcomes:
measure: Change for Office Systolic Blood Pressure (SBP)
timeFrame: From baseline to Day 30
Secondary outcomes:
measure: Change for Office SBP
timeFrame: Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
measure: Change for Office Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
measure: Change for Home Systolic Blood Pressure (SBP)
timeFrame: Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
measure: Change for Home Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
measure: Change for average SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day 30, Day 90
measure: Change for average DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day 30, Day 90
measure: Change for daytime average SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day 30, Day 90
measure: Change for daytime average DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day 30, Day 90
measure: Change for nightime average SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day 30, Day 90
measure: Change for nightime average DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day 30, Day 90
measure: Change for Ankle-Brachial Blood Pressure Index(ABI)
timeFrame: Baseline, Day 90
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety
timeFrame: All AEs over 3 months
measure: Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis
timeFrame: Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
measure: Changes in Intestinal Microbiota Function Pre- and Post-intervention via Metagenomic Analysis
timeFrame: Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
measure: Durability of Engraftment of Donor Microbiome Following FMT
timeFrame: Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
measure: Changes in Intestinal Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
timeFrame: Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
measure: Changes in Serum Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
timeFrame: Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
measure: Change for Fasting Blood Glucose Level
timeFrame: Baseline, Day 90
measure: Change for Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)
timeFrame: Baseline, Day 90
measure: Change for Body Mass Index
timeFrame: Baseline, Day 90
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Shantou
country: China
facility: The Second Affiliated Hospital of Shantou University
state: Guangdong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Shenzhen
country: China
facility: Southern University of Science and Technology Hospital
state: Shenzhen
city: Tianjin
country: China
facility: The People's Hospital of Ji Xian District
state: Tianjin
city: Kunming
country: China
facility: Fuwai Yunnan Cardiovascular Hospital
state: Yunnan
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Jun Cai, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.