Hypertension, Mineralocorticoid Excess
Conditions
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.
Interventions
DRUGEplerenone
Dose escalations of eplerenone 50, 100, or 200mg
DRUGAmlodipine
Dose escalations of amlodipine 2.5, 5, or 10mg
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour systolic ambulatory blood pressure | Change in systolic blood pressure between baseline and 4 weeks on study drug | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAndrea Haas, MD
Brigham and Women's
Outcome results
None listed