Role of LSD1 in Hypertension in Blacks
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- 24-hour systolic ambulatory blood pressure
研究概览
简要总结
Lysine specific demethylase-1 (LSD1) is an epigenetic regulator of gene transcription involved in the pathophysiology of elevated blood pressure and likely renal damage in Blacks. This project investigates whether a genetically driven anti-hypertensive approach proves superior in controlling blood pressure and mitigating renal injury in Blacks who carry the risk allele for LSD1 (rs587168). The findings of these investigations may lead to a new approach in treating a subset (~30%) of the essential hypertension population (Black LSD1 risk allele hypertensives).
详细描述
This proof-of-principle physiologic study in hypertensive Black LSD1 risk allele carriers testing the hypothesis that reductions in blood pressure will be greater with a genetically-driven anti-hypertensive approach (mineralocorticoid receptor antagonist, eplerenone) compared to a non-specific approach (amlodipine). 56 participants will be enrolled in a 12-week randomized, double-blind, active controlled, outpatient study to assess whether eplerenone (LSD1 specific treatment) proves superior in 24-hr ambulatory systolic blood pressure reduction than amlodipine (non-specific treatment). Participants will be randomized to either eplerenone 50mg or amlodipine 2.5mg with escalations in dose of study drug every 4 weeks if the participant's blood pressure is > 140/90.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 17 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •untreated as well as currently treated hypertensives
- •rs587168 allele carriers
- •not on more than two anti-hypertensives
- •normal renal, metabolic, electrolyte, and CBC laboratory tests
- •self-identified Black race
- •age >17 yrs.
排除标准
- •known cardiac disease other than HTN
- •renal, circulatory or neurologic diseases
- •secondary HTN as indicated by history, physical examination or screening blood and urine tests
- •any drug therapy, except for anti-hypertensives and stable thyroid medication replacement
研究组 & 干预措施
Amlodipine Arm
We posit that individuals who carry the LSD1 risk allele have increased mineralocorticoid receptor activity, which results in hypertension. Thus, our mechanistic clinical study will assess whether hypertensive LSD1 risk allele carriers will show significantly greater reductions in blood pressure with a specific aldosterone mediated treatment approach (mineralocorticoid receptor blockade) than with a non-specific approach (amlodipine). To test this hypothesis, we will perform a randomized, double-blind, active controlled study in hypertensive carriers of the LSD1 risk allele using a novel two-limb, proof-of-principle study. Our primary outcome will be a liberal salt diet systolic blood pressure. Therefore, this mechanistic trial will provide support for using a genetic marker that identifies individuals who are uniquely responsive to mineralocorticoid receptor blockade--personalized, precision medicine.
干预措施: Amlodipine (Drug)
Eplerenone Arm
We posit that individuals who carry the LSD1 risk allele have increased mineralocorticoid receptor activity, which results in hypertension. Thus, our mechanistic clinical study will assess whether hypertensive LSD1 risk allele carriers will show significantly greater reductions in blood pressure with a specific aldosterone mediated treatment approach (mineralocorticoid receptor blockade) than with a non-specific approach (amlodipine). To test this hypothesis, we will perform a randomized, double-blind, active controlled study in hypertensive carriers of the LSD1 risk allele using a novel two-limb, proof-of-principle study. Our primary outcome will be a liberal salt diet systolic blood pressure. Therefore, this mechanistic trial will provide support for using a genetic marker that identifies individuals who are uniquely responsive to mineralocorticoid receptor blockade--personalized, precision medicine.
干预措施: Eplerenone (Drug)
结局指标
主要结局
24-hour systolic ambulatory blood pressure
时间窗: Change in systolic blood pressure between baseline and 4 weeks on study drug
Subjects will be counseled regarding liberal salt dietary intake to ensure similar intakes in all subjects \[Na+ (200 mEq), potassium (K+, 100 mEq) and calcium (800 mg)\]. After completion of this diet for 6 days, the subject will collect a 24-hour ambulatory blood pressure. Procedure will be performed before randomization and after 4 weeks of therapy.
次要结局
未报告次要终点
研究者
Andrea Haas, M.D.
Principal Investigator, Instructor of Medicine
Brigham and Women's Hospital