Clinical trial NCT04403347: 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
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Hypertension
Keywords: Hypertension
Microbiome
Treatment
Diet
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2020-05-27
Enrollment: 90
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 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.

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: Baseline, Month 1, Month 2, Month 3
Secondary outcomes:
measure: Change for Office Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Month 1, Month 2, Month 3
measure: Change for daytime average SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Month 1, Month 2, Month 3
measure: Change for daytime average DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Month 1, Month 2, Month 3
measure: Change for nighttime average SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Month 1, Month 2, Month 3
measure: Change for nighttime average DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Month 1, Month 2, Month 3
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety
timeFrame: All AEs over 3 months
measure: Intestinal Microbiota Composition Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metagenomic Analysis
timeFrame: Baseline, Month 1，Month 2，Month 3
measure: Intestinal Microbiota function Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metagenomic Analysis
timeFrame: Baseline, Month 1，Month 2，Month 3
measure: Intestinal and Serum Metabolite Composition Pre- and Post-intervention (innovative dietary formulation, losartan 50mg per day, or usual care) via Metabolomic Analysis
timeFrame: Baseline, Month 1，Month 2，Month 3
measure: Change for Fasting Blood Glucose Level
timeFrame: Baseline, Month 2
measure: Change for Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)
timeFrame: Baseline, Month 2
measure: Change for Body Mass Index
timeFrame: Baseline, Month 2
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: First Affiliated Hospital of Jinan University
state: Guangdong
city: Shantou
country: China
facility: Second Affiliated Hospital of Shantou University Medical College
state: Guangdong
city: Chengdu
country: China
facility: Clinical Medical College&Affiliated Hospital of Chengdu University
state: Sichuan
city: Chongqing
country: China
facility: First Affiliated Hospital of Chongqing Medical University
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: 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.
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.