MR Antagonist and LSD1

Phase 4Active Not RecruitingNCT04840342

Brigham and Women's Hospital300 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

300

Conditions

Hypertension Mineralocorticoid Excess

Interventions

EplerenoneDRUG

Dose escalations of eplerenone 50, 100, or 200mg

AmlodipineDRUG

Dose escalations of amlodipine 2.5, 5, or 10mg

Eligibility

Sex: ALLMin age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * known cardiac disease other than HTN * renal, circulatory or neurologic diseases * diabetes * smoking * secondary HTN as indicated by history, physical examination or screening blood and urine tests * smoking * any drug therapy, except for anti-hypertensives and stable thyroid medication replacement

Locations (1)

Brigham and Women's

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

24-hour systolic ambulatory blood pressure

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.

Time frame: Change in systolic blood pressure between baseline and 4 weeks on study drug

Data from ClinicalTrials.gov

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