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| Name | Class |
|---|---|
| National Natural Science Foundation of China | OTHER_GOV |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FMT capsules | Experimental | 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). |
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| Placebo capsules | Placebo Comparator | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FMT capsules | Biological | Intervention: FMT capsules containing extensively screened donor stool. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change for Office Systolic Blood Pressure (SBP) | Change for Office Systolic Blood Pressure (SBP) | From baseline to Day 30 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| LUYUN FAN | Contact | 01088392165 | fuwai_fanluyun@163.com | |
| LU WANG | Contact | 01088392165 | wanglu@fuwai.com |
| Name | Affiliation | Role |
|---|---|---|
| Jun Cai, MD,PhD | Chinese Academy of Medical Sciences, Fuwai Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fuwai Hospital, Chinese Academy of Medical Sciences | Not yet recruiting | Beijing | Beijing Municipality | 100037 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28143587 | Background | 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. | |
| 28087657 | Background |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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| Placebo capsules | Other | Intervention: Placebo capsules that do not contain donor stool or any active drug. |
|
| 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:
| 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:
| 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:
| 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:
| 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 |
| The Second Affiliated Hospital of Shantou University | Recruiting | Shantou | Guangdong | China |
|
| Qilu Hospital of Shandong University | Recruiting | Jinan | Shandong | China |
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| Shanxi Bethune Hospital | Recruiting | Taiyuan | Shanxi | China |
|
| Southern University of Science and Technology Hospital | Recruiting | Shenzhen | Shenzhen | China |
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| The People's Hospital of Ji Xian District | Not yet recruiting | Tianjin | Tianjin Municipality | China |
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| Fuwai Yunnan Cardiovascular Hospital | Recruiting | Kunming | Yunnan | China |
|
| 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. |
| 32243790 | Background | 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. |
| 40410854 | Derived | Fan L, Chen J, Zhang Q, Ren J, Chen Y, Yang J, Wang L, Guo Z, Bu P, Zhu B, Zhao Y, Wang Y, Liu X, Wang W, Chen Z, Gao Q, Zheng L, Cai J. Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial. Microbiome. 2025 May 23;13(1):133. doi: 10.1186/s40168-025-02118-6. |
| 35209934 | Derived | 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. |