Back to resultsEffect of Gut Microbiome Restoration on Primary Hypertension Via FMT (FMT)
Primary Purpose
Hypertension
Status
Unknown status
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
FMT capsules
Placebo capsules
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension focused on measuring Hypertension, Microbiome, Treatment, Fecal Microbiota Transplantation
Eligibility Criteria
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.
Sites / Locations
- Fuwai Hospital, Chinese Academy of Medical Sciences
- The Second Affiliated Hospital of Shantou UniversityRecruiting
- Qilu Hospital of Shandong UniversityRecruiting
- Shanxi Bethune HospitalRecruiting
- Southern University of Science and Technology HospitalRecruiting
- The People's Hospital of Ji Xian District
- Fuwai Yunnan Cardiovascular HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
FMT capsules
Placebo capsules
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
Change for Office Systolic Blood Pressure (SBP)
Change for Office Systolic Blood Pressure (SBP)
Secondary Outcome Measures
Change for Office SBP
Change for Office SDBP
Change for Office Diastolic Blood Pressure (DBP)
Change for Office Diastolic Blood Pressure (DBP)
Change for Home Systolic Blood Pressure (SBP)
Change for Home Systolic Blood Pressure (SBP)
Change for Home Diastolic Blood Pressure (DBP)
Change for Home Diastolic Blood Pressure (DBP)
Change for average SBP via 24-hour Ambulatory BP Monitoring
Change for average SBP via 24-hour Ambulatory BP Monitoring
Change for average DBP via 24-hour Ambulatory BP Monitoring
Change for average DBP via 24-hour Ambulatory BP Monitoring
Change for daytime average SBP via 24-hour Ambulatory BP Monitoring
Change for daytime average SBP via 24-hour Ambulatory BP Monitoring
Change for daytime average DBP via 24-hour Ambulatory BP Monitoring
Change for daytime average DBP via 24-hour Ambulatory BP Monitoring
Change for nightime average SBP via 24-hour Ambulatory BP Monitoring
Change for nightime average SBP via 24-hour Ambulatory BP Monitoring
Change for nightime average DBP via 24-hour Ambulatory BP Monitoring
Change for nightime average DBP via 24-hour Ambulatory BP Monitoring
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.
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Number of Participants with Adverse Events (AEs) as a Measure of Safety
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
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
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
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
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
Change for Fasting Blood Glucose Level
Change for Fasting Blood Glucose Level
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)
Change for Body Mass Index
Change for Body Mass Index
Full Information
NCT ID
NCT04406129
First Posted
May 20, 2020
Last Updated
July 10, 2021
Sponsor
Chinese Academy of Medical Sciences, Fuwai Hospital
Collaborators
National Natural Science Foundation of China
1. Study Identification
Unique Protocol Identification Number
NCT04406129
Brief Title
Effect of Gut Microbiome Restoration on Primary Hypertension Via FMT
Acronym
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
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 17, 2021 (Actual)
Primary Completion Date
February 1, 2022 (Anticipated)
Study Completion Date
September 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences, Fuwai Hospital
Collaborators
National Natural Science Foundation of China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Hypertension, Microbiome, Treatment, Fecal Microbiota Transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
FMT capsules
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo capsules
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Biological
Intervention Name(s)
FMT capsules
Intervention Description
Intervention: FMT capsules containing extensively screened donor stool.
Intervention Type
Other
Intervention Name(s)
Placebo capsules
Intervention Description
Intervention: Placebo capsules that do not contain donor stool or any active drug.
Primary Outcome Measure Information:
Title
Change for Office Systolic Blood Pressure (SBP)
Description
Change for Office Systolic Blood Pressure (SBP)
Time Frame
From baseline to Day 30
Secondary Outcome Measure Information:
Title
Change for Office SBP
Description
Change for Office SDBP
Time Frame
Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
Title
Change for Office Diastolic Blood Pressure (DBP)
Description
Change for Office Diastolic Blood Pressure (DBP)
Time Frame
Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
Title
Change for Home Systolic Blood Pressure (SBP)
Description
Change for Home Systolic Blood Pressure (SBP)
Time Frame
Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
Title
Change for Home Diastolic Blood Pressure (DBP)
Description
Change for Home Diastolic Blood Pressure (DBP)
Time Frame
Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
Title
Change for average SBP via 24-hour Ambulatory BP Monitoring
Description
Change for average SBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day 30, Day 90
Title
Change for average DBP via 24-hour Ambulatory BP Monitoring
Description
Change for average DBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day 30, Day 90
Title
Change for daytime average SBP via 24-hour Ambulatory BP Monitoring
Description
Change for daytime average SBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day 30, Day 90
Title
Change for daytime average DBP via 24-hour Ambulatory BP Monitoring
Description
Change for daytime average DBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day 30, Day 90
Title
Change for nightime average SBP via 24-hour Ambulatory BP Monitoring
Description
Change for nightime average SBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day 30, Day 90
Title
Change for nightime average DBP via 24-hour Ambulatory BP Monitoring
Description
Change for nightime average DBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day 30, Day 90
Title
Change for Ankle-Brachial Blood Pressure Index(ABI)
Description
Change for ABI as an objective measurement of arterial insufficiency based on the ratio of ankle systolic pressure to brachial systolic pressure.
Time Frame
Baseline, Day 90
Title
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Description
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Time Frame
All AEs over 3 months
Title
Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis
Description
Changes in Intestinal Microbiota Composition Pre- and Post-intervention (FMT or Placebo) via Metagenomic Analysis, stratified by:
Randomisation
Change in Office SBP
Time Frame
Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
Title
Changes in Intestinal Microbiota Function Pre- and Post-intervention via Metagenomic Analysis
Description
Changes in Intestinal Microbiota Function Pre- and Post-intervention (FMT or Placebo) via Metagenomic Analysis, stratified by:
Randomisation
Change in Office SBP
Time Frame
Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
Title
Durability of Engraftment of Donor Microbiome Following FMT
Description
Durability of engraftment of donor microbiome following FMT, measured by similarity comparison of intestinal microbiota composition between donor and recipient
Time Frame
Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
Title
Changes in Intestinal Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
Description
Changes in Intestinal Metabolite Composition Pre- and Post-intervention (FMT or Placebo) via Metabolomic Analysis, stratified by:
Randomisation
Change in Office SBP
Time Frame
Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
Title
Changes in Serum Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
Description
Changes in Serum Metabolite Composition Pre- and Post-intervention (FMT or Placebo) via Metabolomic Analysis, stratified by:
Randomisation
Change in Office SBP
Time Frame
Baseline, Day 7, Day 14, Day 30, Day 60, Day 90
Title
Change for Fasting Blood Glucose Level
Description
Change for Fasting Blood Glucose Level
Time Frame
Baseline, Day 90
Title
Change for Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)
Description
Change for Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)
Time Frame
Baseline, Day 90
Title
Change for Body Mass Index
Description
Change for Body Mass Index
Time Frame
Baseline, Day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
LUYUN FAN
Phone
01088392165
Email
fuwai_fanluyun@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
LU WANG
Phone
01088392165
Email
wanglu@fuwai.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Cai, MD,PhD
Organizational Affiliation
Chinese Academy of Medical Sciences, Fuwai Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fuwai Hospital, Chinese Academy of Medical Sciences
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100037
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Cai
Facility Name
The Second Affiliated Hospital of Shantou University
City
Shantou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Youren Chen
Facility Name
Qilu Hospital of Shandong University
City
Jinan
State/Province
Shandong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peili Bu
Facility Name
Shanxi Bethune Hospital
City
Taiyuan
State/Province
Shanxi
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Ren
Facility Name
Southern University of Science and Technology Hospital
City
Shenzhen
State/Province
Shenzhen
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bingpo Zhu
Facility Name
The People's Hospital of Ji Xian District
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jinfeng Yang
Facility Name
Fuwai Yunnan Cardiovascular Hospital
City
Kunming
State/Province
Yunnan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zihong Guo
12. IPD Sharing Statement
Citations:
PubMed Identifier
28143587
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.
Results Reference
background
PubMed Identifier
28087657
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.
Results Reference
background
PubMed Identifier
32243790
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.
Results Reference
background
PubMed Identifier
35209934
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.
Results Reference
derived
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Effect of Gut Microbiome Restoration on Primary Hypertension Via FMT
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