MR Antagonist and LSD1

Hypertension Clinical Trial

Official title:

Role of LSD1 in Hypertension in Blacks

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04840342
• Other study ID #: 2021p000990
• Status: Recruiting
• Phase: Phase 4
• Start date: February 3, 2022
• Est. completion date: June 2026

Study information

• Verified date: July 2023
• Source: Brigham and Women's Hospital
• Contact: Andrea Haas, MD
• Phone: 6177325666
• Email: ahaas2[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: June 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hyperaldosteronism
• Hypertension
• Mineralocorticoid Excess

Intervention

Drug:
• Eplerenone
Dose escalations of eplerenone 50, 100, or 200mg
• Amlodipine
Dose escalations of amlodipine 2.5, 5, or 10mg

Locations

Country	Name	City	State
United States	Brigham and Women's	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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