MR Antagonist and LSD1

Role of LSD1 in Hypertension in Blacks

Sponsorzy

Główny sponsor: Brigham and Women's Hospital

Źródło Brigham and Women's Hospital
Krótkie podsumowanie

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).

szczegółowy opis

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.

Ogólny stan Not yet recruiting
Data rozpoczęcia 2021-07-01
Data zakończenia 2026-06-01
Podstawowa data ukończenia 2026-02-01
Faza Phase 4
Typ studiów Interventional
Wynik podstawowy
Pomiar Ramy czasowe
24-hour systolic ambulatory blood pressure Change in blood pressure between baseline and 4 weeks on study drug
Rekrutacja 300
Stan: schorzenie
Interwencja

Rodzaj interwencji: Drug

Nazwa interwencji: Eplerenone

Opis: Dose escalations of eplerenone 50, 100, or 200mg

Etykieta grupy ramion: Eplerenone Arm

Rodzaj interwencji: Drug

Nazwa interwencji: Amlodipine

Opis: Dose escalations of amlodipine 2.5, 5, or 10mg

Etykieta grupy ramion: Amlodipine Arm

Kwalifikowalność

Kryteria:

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; and 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.

Płeć:

All

Minimalny wiek:

17 Years

Maksymalny wiek:

N/A

Zdrowi wolontariusze:

No

Data weryfikacji

2021-04-01

Odpowiedzialna impreza

Rodzaj: Principal Investigator

Powiązanie badacza: Brigham and Women's Hospital

Pełne imię i nazwisko badacza: Andrea Haas, M.D.

Tytuł badacza: Instructor of Medicine

Ma rozszerzony dostęp No
Przeglądanie warunków
Liczba ramion 2
Grupa Arm

Etykieta: Eplerenone Arm

Rodzaj: Experimental

Opis: 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.

Etykieta: Amlodipine Arm

Rodzaj: Experimental

Opis: 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.

Dane pacjenta No
Badanie informacji o projekcie

Przydział: Randomized

Model interwencji: Parallel Assignment

Podstawowy cel: Treatment

Maskowanie: Triple (Participant, Investigator, Outcomes Assessor)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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