Antihypertensive Mechanisms of Minocycline in Resistant Hypertension: Role of the Gut Microbiota-brain-immune Axis
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Gut microbiome
研究概览
简要总结
The goal of this clinical trial is to learn about the mechanisms by which minocycline effect blood pressure in individuals with treatment-resistant hypertension. The main questions it aims to answer are:
- To what extent does minocycline lower blood pressure?
- Are such blood pressure effects mediated through changes in gut microbiota, gut leakiness, systemic inflammation, neuroinflammation, or some combination of these?
Participants will be randomly assigned to treatment with minocycline or placebo, treated daily for 3 months, to evaluate these questions.
详细描述
One hundred twenty patients with treatment-resistant hypertension will be enrolled. A total of 34 patients (17 from each treatment arm), who are participants in the main study, will also be enrolled in a substudy that includes neuroimaging. The study will last 3 months, and will include 3 visit time points (screening, randomization visit, 3-month follow-up visit).
Participants will be randomly assigned, in a 1:1 allocation, to minocycline 100 mg twice per day, or matching placebo, each provided by the study, and investigators will be blinded to treatment assignment.
At the baseline and 3-month follow-up visit, subjects will undergo:
- A comprehensive medical history and examination, including assessment of antihypertensive treatment history
- A series of behavioral activity questionnaires
- Blood tests (plasma renin activity, aldosterone, catecholamines, serum creatinine, lipid panel, hemoglobin a1c, as well as various biomarkers of immune and inflammatory activity, and gut leakiness markers)
- Urine/saliva tests for antihypertensive adherence
- Gut microbiota profiling via whole metagenomic sequencing of stool samples
- Blood pressure (BP) measurement, including unattended office BP and 24-hour ambulatory BP
Subjects enrolled in the neuroimaging substudy will also have PET/MR imaging performed at each visit. Neuroimaging activities will take place at Emory University in Atlanta, GA.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Uncontrolled TRH, defined as uncontrolled blood pressure (mean 24-hour ambulatory systolic BP ≥125 mm Hg or diastolic BP ≥80 mm Hg) while being adherent to a stable (no changes in ≥14 days prior) antihypertensive regimen of 3 or more drugs, including an adequately dosed diuretic or unable to tolerate a diuretic.
- •The participant agrees to have all study procedures performed
排除标准
- •Known hypersensitivity or contraindication to minocycline or other tetracyclines
- •Recent (≤3 months prior), ongoing, or expected use of oral antibiotics
- •Estimated glomerular filtration rate (eGFR) of <45mL/min/1.73m2, using the MDRD equation
- •Known secondary hypertension
- •History of hypertensive crisis, defined as any in-patient hospitalizations for hypertensive crisis/emergency within the past year
- •History of orthostatic hypotension, defined as two or more episode(s) of orthostatic hypotension (reduction of SBP of >20 mm Hg or DBP of >10 mm Hg within 3 minutes of standing) in the past year
- •History of myocardial infarction, unstable angina, syncope, or cerebrovascular accident in prior 6 months
- •Evidence of alcoholism or drug abuse
- •Severe comorbid conditions (i.e., neoplasms or HIV positive or AIDS)
- •Current pregnancy or anticipated pregnancy during the study.
研究组 & 干预措施
Minocycline Hydrochloride
Minocycline hydrochloride 100 mg, administered twice daily for 3 months
干预措施: Minocycline Hydrochloride (Drug)
Placebo
Placebo administered twice daily for 3 months
干预措施: Placebo (Drug)
结局指标
主要结局
Gut microbiome
时间窗: 3 months
Change in butyrate-producing gene abundance
24-h systolic blood pressure
时间窗: 3 months
Change in mean 24-hour ambulatory systolic blood pressure
Gut inflammation and leakiness
时间窗: 3 months
Change in gut-homing inflammatory T-helper cells
Neuroinflammation
时间窗: 3 months
Change in \[18F\]FEPPA radiotracer uptake on PET/MR imaging
次要结局
- 24-h heart rate(3 months)
- Mucin-degrading gene abundance(3 months)
- IgA+ coated plasma cells(3 months)
- Gut leakiness markers(3 months)
- 24-h diastolic blood pressure(3 months)
- Adverse Events(3 months)