MR Antagonist and LSD1

NCT04840342 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: 2021p000990
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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).

Conditions

Hypertension; Mineralocorticoid Excess

Outcome Measures

Primary Outcomes (1)

• 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.

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

Study Arms (2)

Eplerenone Arm

EXPERIMENTAL

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.

Drug: Eplerenone

Amlodipine Arm

EXPERIMENTAL

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.

Drug: Amlodipine

Interventions

Eplerenone DRUG

Dose escalations of eplerenone 50, 100, or 200mg

Eplerenone Arm

Amlodipine DRUG

Dose escalations of amlodipine 2.5, 5, or 10mg

Amlodipine Arm

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Hypertension; Hyperaldosteronism

Interventions

Eplerenone; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Andrea Haas, MD

  Brigham and Women's

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Instructor of Medicine

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: April 12, 2021
• Study Start: February 3, 2022
• Primary Completion: September 15, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 29, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)