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Effect of Gut Microbiome Restoration on Primary Hypertension Via Dietary Intervention

Primary Purpose

Hypertension

Status

Recruiting

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

Innovative Dietary Formulation (Patent ID: CN110250417A)

Losartan 50mg per day

About this trial

This is an interventional treatment trial for Hypertension focused on measuring Hypertension, Microbiome, Treatment, Diet

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

First Affiliated Hospital of Jinan UniversityRecruiting
Second Affiliated Hospital of Shantou University Medical CollegeRecruiting
Clinical Medical College&Affiliated Hospital of Chengdu UniversityRecruiting
First Affiliated Hospital of Chongqing Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

No Intervention

Arm Label

Innovative Dietary Formulation

Antihypertensive Medication

Usual Care

Arm Description

In addition to regular diets and usual care of hypertension, additional innovative dietary formulation will be orally taken 3 times per day.

In addition to regular diets and usual care of hypertension, antihypertensive medication will be orally taken (Losartan 50mg per day).

Usual Care (Guideline-based patient education and lifestyle recommendations)

Outcomes

Primary Outcome Measures

Change for Office Systolic Blood Pressure (SBP)

Secondary Outcome Measures

Change for Office Diastolic Blood Pressure (DBP)

Change for daytime average SBP via 24-hour Ambulatory BP Monitoring

Change for daytime average DBP via 24-hour Ambulatory BP Monitoring

Change for nighttime average SBP via 24-hour Ambulatory BP Monitoring

Change for nighttime average DBP via 24-hour Ambulatory BP Monitoring

Number of Participants with Adverse Events (AEs) as a Measure of Safety

Intestinal Microbiota Composition Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metagenomic Analysis

Intestinal Microbiota function Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metagenomic Analysis

Intestinal and Serum Metabolite Composition Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metabolomic Analysis

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 Body Mass Index

Full Information

NCT ID

NCT04403347

First Posted

May 20, 2020

Last Updated

October 20, 2022

Sponsor

Chinese Academy of Medical Sciences, Fuwai Hospital

Collaborators

National Natural Science Foundation of China

1. Study Identification

Unique Protocol Identification Number

NCT04403347

Brief Title

Effect of Gut Microbiome Restoration on Primary Hypertension Via Dietary Intervention

Official Title

Effect of Innovative Natural Dietary Formulation on Primary Hypertension and the Underlying Mechanism of Gut Microbiome Restoration: Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

July 8, 2021 (Actual)

Primary Completion Date

January 31, 2023 (Anticipated)

Study Completion Date

September 30, 2023 (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

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Mounting preclinical and clinical evidences have proved the optimal role of diets (i.e. DASH (Dietary Approaches to Stop Hypertension) diet, Mediterranean diet) on BP control and a causal role of gut microbiota on the pathogenesis of primary hypertension. Dietary changes appeared to reshape gut microbiota and to ameliorate diseases such as Type 2 Diabetes. A hypothesis is thus raised that dietary changes can be a potential approach to ameliorate hypertension via gut microbiome restoration. This pilot study will utilize an innovative natural dietary formulation (patent ID: CN110250417A), in comparison with classic antihypertensive treatment (losartan 50mg per day) and usual care (guideline-based patient education and lifestyle recommendations), to investigate its effect and safety on primary hypertension treatment, and the underlying mechanisms of gut microbiome restoration.

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 methodologies, effect, safety and underlying mechanisms of gut microbiome restoration on hypertension. These pilot studies also present as the clinical translational part 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 Pilot Study II: Objective: With reference of DASH diet and Mediterranean diet, this study aims to explore the effect and safety of an innovative natural dietary formulation on primary hypertension, and the underlying mechanisms of gut microbiome restoration. Study Design: A multicenter, randomized, open-label, positive- and negative- 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, Diet

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Innovative Dietary Formulation

Arm Type

Experimental

Arm Description

In addition to regular diets and usual care of hypertension, additional innovative dietary formulation will be orally taken 3 times per day.

Arm Title

Antihypertensive Medication

Arm Type

Active Comparator

Arm Description

In addition to regular diets and usual care of hypertension, antihypertensive medication will be orally taken (Losartan 50mg per day).

Arm Title

Usual Care

Arm Type

No Intervention

Arm Description

Usual Care (Guideline-based patient education and lifestyle recommendations)

Intervention Type

Dietary Supplement

Intervention Name(s)

Innovative Dietary Formulation (Patent ID: CN110250417A)

Intervention Description

In addition to regular diets and usual care of hypertension, additional innovative natural dietary formulation derived from tartary buckwheat will be orally taken 3 times per day.

Intervention Type

Drug

Intervention Name(s)

Losartan 50mg per day

Other Intervention Name(s)

Antihypertensive Medication

Intervention Description

In addition to regular diets and usual care of hypertension, antihypertensive medication will be orally taken (Losartan 50mg per day).

Primary Outcome Measure Information:

Title

Change for Office Systolic Blood Pressure (SBP)

Description

Change for Office Systolic Blood Pressure (SBP)

Time Frame

Baseline, Month 1, Month 2, Month 3

Secondary Outcome Measure Information:

Title

Change for Office Diastolic Blood Pressure (DBP)

Description

Change for Office Diastolic Blood Pressure (DBP)

Time Frame

Baseline, Month 1, Month 2, Month 3

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, Month 1, Month 2, Month 3

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, Month 1, Month 2, Month 3

Title

Change for nighttime average SBP via 24-hour Ambulatory BP Monitoring

Description

Change for nighttime average SBP via 24-hour Ambulatory BP Monitoring

Time Frame

Baseline, Month 1, Month 2, Month 3

Title

Change for nighttime average DBP via 24-hour Ambulatory BP Monitoring

Description

Change for nighttime average DBP via 24-hour Ambulatory BP Monitoring

Time Frame

Baseline, Month 1, Month 2, Month 3

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

Intestinal Microbiota Composition Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metagenomic Analysis

Description

Intestinal Microbiota Composition Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metagenomic Analysis

Time Frame

Baseline, Month 1，Month 2，Month 3

Title

Intestinal Microbiota function Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metagenomic Analysis

Description

Intestinal Microbiota function Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metagenomic Analysis

Time Frame

Baseline, Month 1，Month 2，Month 3

Title

Intestinal and Serum Metabolite Composition Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metabolomic Analysis

Description

Intestinal and Serum Metabolite Composition Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metabolomic Analysis

Time Frame

Baseline, Month 1，Month 2，Month 3

Title

Change for Fasting Blood Glucose Level

Description

Change for Fasting Blood Glucose Level

Time Frame

Baseline, Month 2

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, Month 2

Title

Change for Body Mass Index

Description

Change for Body Mass Index

Time Frame

Baseline, Month 2

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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, MD

Phone

01088392165

fuwai_fanluyun@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

LU WANG

Phone

01088392165

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

First Affiliated Hospital of Jinan University

City

Guangzhou

State/Province

Guangdong

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jun Guo

Facility Name

Second Affiliated Hospital of Shantou University Medical College

City

Shantou

State/Province

Guangdong

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Youren Chen

Facility Name

Clinical Medical College&Affiliated Hospital of Chengdu University

City

Chengdu

State/Province

Sichuan

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yamei Zhang

Facility Name

First Affiliated Hospital of Chongqing Medical University

City

Chongqing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Qifu Li

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

29590046

Citation

Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, Fu H, Xue X, Lu C, Ma J, Yu L, Xu C, Ren Z, Xu Y, Xu S, Shen H, Zhu X, Shi Y, Shen Q, Dong W, Liu R, Ling Y, Zeng Y, Wang X, Zhang Q, Wang J, Wang L, Wu Y, Zeng B, Wei H, Zhang M, Peng Y, Zhang C. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018 Mar 9;359(6380):1151-1156. doi: 10.1126/science.aao5774.

Results Reference

background

PubMed Identifier

27927713

Citation

Marques FZ, Nelson E, Chu PY, Horlock D, Fiedler A, Ziemann M, Tan JK, Kuruppu S, Rajapakse NW, El-Osta A, Mackay CR, Kaye DM. High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice. Circulation. 2017 Mar 7;135(10):964-977. doi: 10.1161/CIRCULATIONAHA.116.024545. Epub 2016 Dec 7.

Results Reference

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Effect of Gut Microbiome Restoration on Primary Hypertension Via Dietary Intervention

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