Effect and Safety of Intensive Fecal Microbiota Transplantation on Primary Hypertension: a Randomized Clinical Trial.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 72
- 试验地点
- 3
- 主要终点
- Change in Office Systolic Blood Pressure (SBP)
研究概览
简要总结
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 study will perform intense fecal microbiota transplantation (FMT) intervention via oral capsules, in comparison with placebo capsules, to investigate the effect, safety and underlying mechanisms of gut microbiome intervention on primary hypertension.
详细描述
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, a casual role of gut microbiome disorder was observed in primary hypertension (Microbiome. 2017;5(1):14.), and trend of ameliorating SBP was observed after short-course FMT intervention but recovery after intervention termination(Trials. 2022;23(1):178, unpublished results). The investigators therefore developed a consecutive study of intensive FMT intervention on primary hypertension.
Objective
To explore the effect, safety and underlying mechanisms of intensive FMT on primary hypertension.
Study Design: A multi-center, randomized, 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.
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, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18~65 years.
- •Established Diagnosis of Grade 1 Hypertension (initial diagnosis or free from antihypertensive drugs within a month): 140mmHg≤ Office SBP<160mmHg and/or 90mmHg≤ Office DBP<100mmHg 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.
排除标准
- •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.
结局指标
主要结局
Change in Office Systolic Blood Pressure (SBP)
时间窗: From baseline to Week 8
Change in Office Systolic Blood Pressure (SBP)
次要结局
- Change in Office Diastolic Blood Pressure (DBP)(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12)
- Change in daytime DBP via 24-hour Ambulatory BP Monitoring(Baseline, Week 4, Week 8, Week 12)
- Change in Body Mass Index(Baseline, Week 4, Week 8, Week 12)
- Change in Office Systolic Blood Pressure (SBP)(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 12)
- Change in average SBP via 24-hour Ambulatory BP Monitoring(Baseline, Week 4, Week 8, Week 12)
- Change in nighttime SBP via 24-hour Ambulatory BP Monitoring(Baseline, Week 4, Week 8, Week 12)
- Change in average DBP via 24-hour Ambulatory BP Monitoring(Baseline, Week 4, Week 8, Week 12)
- Change in daytime SBP via 24-hour Ambulatory BP Monitoring(Baseline, Week 4, Week 8, Week 12)
- Change in Home Systolic Blood Pressure (SBP)(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12)
- Change in Home Diastolic Blood Pressure (DBP)(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12)
- Change in nighttime DBP via 24-hour Ambulatory BP Monitoring(Baseline, Week 4, Week 8, Week 12)
- Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis(Baseline, Week 4, Week 8, Week 12)
- Change in Fasting Blood Glucose Level(Baseline, Week 4, Week 8, Week 12)
- Number of Participants with Adverse Events (AEs) as a Measure of Safety(All AEs over 12 weeks)
- Changes in Intestinal Microbiota function revealed by KEGG pathways and KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis(Baseline, Week 4, Week 8, Week 12)
- Changes in Plasma Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis(Baseline, Week 4, Week 8, Week 12)
- Change in blood HbA1c level(Baseline, Week 4, Week 8, Week 12)
- Change in blood lipid level(Baseline, Week 4, Week 8, Week 12)
- Durability of Engraftment of Donor Microbiome Following FMT(Baseline, Week 4, Week 8, Week 12)
研究者
Jun Cai
Professor, Doctoral supervisor, Assistant Principal of Fuwai Hospital, Chief of Hypertension Center, Fuwai Hospital,PUMC&CAMS
Chinese Academy of Medical Sciences, Fuwai Hospital