The Role of Gut Microbiota in Hypertension: Brain-Gut Microbiome-Immune Axis in Hypertension
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 292
- 试验地点
- 1
- 主要终点
- Characterize gut microbiota composition at genus level
研究概览
简要总结
Hypertension is the single most prevalent risk factor for heart diseases, heart failure, kidney failure and stroke. About 1 in 3 adults in the United States have hypertension. Approximately 28-30% of hypertensive patients suffer from resistant hypertension (RH). Inflammation has been implicated in the pathogenesis of the hypertension. Additional data suggests the involvement of gut microbiota in host normal cardiovascular functions and pathophysiology. Accumulating evidence demonstrates that antibiotic treatment benefits patients with acute coronary syndromes and reduces the incidence of ischemic cardiovascular events. Even though these studies did not address effects of antibiotic treatment on the gut microbiota, it is possible that gut microbiota could affect neurologic inflammation. Finally, intestinal microbiota has recently been proposed to modulate blood pressure (BP) through production of short-chain fatty acids. In order to investigate this, the investigators hypothesize that gut microbiota is involved in the neuroinflammation-mediated initiation and establishment of RH, and targeting gut microbiota by minocycline would produce beneficial outcomes in RH.
详细描述
This is a prospective cohort design. This study will enroll 388 subjects: 81 patients without HTN as a reference group, 81 patients with controlled HTN, 55 patients with uncontrolled HTN, 55 with remodeled RH, and 81 patients with RH to characterize gut microbiota composition. Subjects will provide stool samples for analysis. Subjects will also provide a blood sample for inflammatory marker and stem cell analysis.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age >18 and <80
- •is competent and willing to provide consent
- •Inclusion criteria for each subject group:
- •Control subjects will have a systolic BP <140mmHg with no cardiovascular disease
- •Patients with controlled hypertension
- •Patients with uncontrolled hypertension
- •Resistant hypertension subjects will have systolic blood pressure (BP) ≥140 mmHg despite ≥3 anti-hypertensive medications of different classes one of which should be a diuretic
- •Patients who are no longer RH subjects and have normal blood pressure
- •Subjects participating in NCT 02133872 will be eligible to participate
排除标准
- •currently pregnant or have been pregnant in the last 6 months;
- •antibiotic treatment within 2 months of study enrollment;
- •currently taking a medication (e.g., antibiotic, anti-inflammatory agents, glucocorticoids or other immune modulating medications);
- •unwilling to discontinue vitamin or supplements, including probiotics, potentially affecting gut microbiota (vitamins/supplements and medications that possibly affect the gut microbiota should be discontinued for at least 2wks prior to stool collection);
- •history of intestinal surgery, inflammatory bowel disease, celiac disease, lactose intolerance, chronic pancreatitis or other malabsorption disorder.
结局指标
主要结局
Characterize gut microbiota composition at genus level
时间窗: 24 hours
Stool samples to analyze the composition of the microbiota, extracted bacterial genomic DNA will be used as a template for PCR reactions targeting the V4-V5 variable regions of the 16S rRNA gene. Amplicons generated from the PCR will be run on the Illumina MiSeq sequencing platform available in our laboratory to profile microbial communities at genus level.
Characterize gut microbiota composition at phylum level
时间窗: 24 hours
Stool samples to analyze the composition of the microbiota, extracted bacterial genomic DNA will be used as a template for PCR reactions targeting the V4-V5 variable regions of the 16S rRNA gene. Amplicons generated from the PCR will be run on the Illumina MiSeq sequencing platform available in our laboratory to profile microbial communities at phylum level.
次要结局
- Reduction in BP is associated with changes in gut microbiota composition in RH subjects.(Baseline, 3 months)
- IS hypertension associated with increased sympathetic activity and decreased parasympathetic activity and whether minocycline or other tetracyclines are effective to improve this balance(Baseline and 3 months)
- To determine if characterization of gut microbiota in at risk patients predicts long term care utilization and/or cardiovascular outcomes(Up to 5 years)