MR Antagonist and LSD1

NCT ID: NCT04840342

Last Updated: 2025-11-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-03
• Study Completion Date: 2026-06-30

Brief Summary

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).

Detailed Description

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.

Conditions

Hypertension; Mineralocorticoid Excess

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Amlodipine

Intervention Type: DRUG

Dose escalations of amlodipine 2.5, 5, or 10mg

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.

Group Type: EXPERIMENTAL

Eplerenone

Intervention Type: DRUG

Dose escalations of eplerenone 50, 100, or 200mg

Interventions

Eplerenone

Dose escalations of eplerenone 50, 100, or 200mg

Intervention Type: DRUG

Amlodipine

Dose escalations of amlodipine 2.5, 5, or 10mg

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Andrea Haas, M.D.

Principal Investigator, Instructor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrea Haas, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's

Locations

Brigham and Women's

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2021p000990

Identifier Type: -

Identifier Source: org_study_id