Back to resultsMR Antagonist and LSD1
Primary Purpose
Hypertension, Mineralocorticoid Excess
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Eplerenone
Amlodipine
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension
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
Sites / Locations
- Brigham and Women'sRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Eplerenone Arm
Amlodipine Arm
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT04840342
First Posted
April 7, 2021
Last Updated
July 27, 2023
Sponsor
Brigham and Women's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04840342
Brief Title
MR Antagonist and LSD1
Official Title
Role of LSD1 in Hypertension in Blacks
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 3, 2022 (Actual)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
June 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Mineralocorticoid Excess
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Eplerenone Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Amlodipine Arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Eplerenone
Intervention Description
Dose escalations of eplerenone 50, 100, or 200mg
Intervention Type
Drug
Intervention Name(s)
Amlodipine
Intervention Description
Dose escalations of amlodipine 2.5, 5, or 10mg
Primary Outcome Measure Information:
Title
24-hour systolic ambulatory blood pressure
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Haas, MD
Phone
6177325666
Email
ahaas2@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Haas, MD
Organizational Affiliation
Brigham and Women's
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Haas, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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MR Antagonist and LSD1
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