Effect of Probiotics on Grade 1 Primary Hypertension and Prehypertension and the Underlying Mechanism: a Randomized Controlled Trial
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 115
- 试验地点
- 6
- 主要终点
- Change in Office Systolic Blood Pressure (SBP)
研究概览
简要总结
Gut microbiota was found to play a causal role in the pathogenesis of hypertension. Probiotics were shown to have a potential anti-hypertensive effect in human/rodent studies. This study aims to explore the effect, safety, and underlying mechanisms of the combination of probiotics, containing 10 strains from Lactobacillus and Bifidobacterium, on hypertension, compared with placebo.
详细描述
Background: Primary hypertension is the leading risk factor of cardiovascular diseases and all-cause mortality, and contributes to severe global health burden. Emerging evidence has shown a close association between gut microbiota and hypertension. Fecal transplantation from hypertensive patients/animals to germ-free mice caused elevation of blood pressure, indicating a causal role of gut dysbiosis in hypertension. Probiotics were found to have a potential anti-hypertensive effect in both human and rodent studies. Based on the investigators' previous findings of metagenomics analysis of hypertensive, prehypertensive patients and healthy control, hypertensive and prehypertensive patients were lack of probiotics. Therefore, the investigators developed this study to explore the effect, safety, and underlying mechanisms of the combination of probiotics, containing 10 strains from Lactobacillus and Bifidobacterium, on hypertension, compared with placebo.
Objective
To explore the effect, safety, and underlying mechanisms of the combination of probiotics on grade 1 primary hypertension and prehypertension.
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 in analyzing data and a third party to supervise data quality.
Ethics: The Ethics Committee of Fuwai Hospital approved this study. Informed consent before patient enrollment is required.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18~60 years.
- •Grade 1 hypertension and part of prehypertension (initial diagnosis or free from antihypertensive drugs within 2 weeks): 130 mmHg ≤ Average office SBP < 160 mmHg, and/or 85 mmHg ≤ Average office DBP < 100 mmHg, according to the "2018 Chinese Guidelines for Prevention and Treatment of Hypertension" and "National guideline for hypertension management in China (2019)".
- •Patients with informed consent after thorough explanation.
排除标准
- •Antibiotics or probiotics usage within the last 2 weeks.
- •Participants of other clinical trials currently or within last 3 months.
- •Antihypertensive medications usage currently or within last 2 weeks.
- •Diagnosed secondary hypertension
- •History of diabetes mellitus.
- •History of peripheral atherosclerosis.
- •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 stroke (not including lacunar infarction and transient ischemic attack [TIA]).
- •History of coronary heart disease.
- •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.
- •With special diet habits, such as vegetarians.
- •Active gastritis or enteritis; gastrointestinal ulcers or bleeding; post-gastrointestinal surgery, such as intestinal excision.
- •Other conditions inappropriate for recruitment according to the investigators.
结局指标
主要结局
Change in Office Systolic Blood Pressure (SBP)
时间窗: From baseline to day 56
Change in Office Systolic Blood Pressure (SBP)
次要结局
- Change in Body Mass Index(Baseline, Day 56)
- Change in Blood Uric Acid(Baseline, Day 56)
- Change in daytime average DBP via 24-hour Ambulatory BP Monitoring(Baseline, Day28, Day 56, Day 84)
- Change in daytime average SBP via 24-hour Ambulatory BP Monitoring(Baseline, Day28, Day 56, Day 84)
- Change in Office Diastolic Blood Pressure (DBP)(Baseline, Day28, Day 56, Day 84)
- Change in average DBP via 24-hour Ambulatory BP Monitoring(Baseline, Day28, Day 56, Day 84)
- Number of Participants with Adverse Events (AEs) as a Measure of Safety(Baseline, Day28, Day 56, Day 84)
- Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis(Baseline, Day28, Day 56, Day 84)
- Change in nightime average DBP via 24-hour Ambulatory BP Monitoring(Baseline, Day28, Day 56, Day 84)
- Changes in Serum Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis(Baseline, Day28, Day 56, Day 84)
- Change in Office SBP(Baseline, Day28, Day 56, Day 84)
- Change in average SBP via 24-hour Ambulatory BP Monitoring(Baseline, Day28, Day 56, Day 84)
- Change in nightime average SBP via 24-hour Ambulatory BP Monitoring(Baseline, Day28, Day 56, Day 84)
- Changes in Intestinal Microbiota Function Pre- and Post-intervention via Metagenomic Analysis(Baseline, Day28, Day 56, Day 84)
- Changes in Intestinal Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis(Baseline, Day28, Day 56, Day 84)
- Change in Fasting Blood Glucose Level(Baseline, Day 56)
- Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)(Baseline, Day 56)
研究者
Jun Cai
Professor, Director of Hypertension Center
Chinese Academy of Medical Sciences, Fuwai Hospital