Striatin genotype-based, mineralocorticoid receptor antagonist-driven clinical trial: study rationale and design.
Pharmacogenet Genomics
; 31(4): 83-88, 2021 06 01.
Article
em En
| MEDLINE
| ID: mdl-33904521
ABSTRACT
OBJECTIVES:
In human studies and genetically altered mouse studies, variants in the striatin gene (STRN) are associated with increased blood pressure (BP) and aldosterone on a liberal salt diet. This clinical trial is based on the presumed mechanism for striatin-associated HTN - increased aldosterone. It is designed to determine if participants with the STRN risk alleles will have a greater BP reduction on a liberal salt diet with a specific, mechanism-based therapy - a mineralocorticoid receptor antagonist, eplerenone - as compared with a nonspecific anti-hypertensive therapy - amlodipine.METHODS:
One hundred five hypertensive adults with the STRN risk alleles (SNP rs2540923 carriers or rs888083 homozygotes) will be enrolled in a 12-week, double-blind, dose-escalation, clinical trial. After a minimum 2-week washout period and baseline assessment of BP on a liberal salt diet, participants will be randomized to either daily eplerenone or amlodipine. Participants will take daily at-home BP recordings as a safety check. After 4 and 8 weeks of drug therapy, BP will be measured by the study team and medication will be increased, if needed, to achieve a participant goal BP of <140/90 mmHg.Anticipated results We anticipate that STRN risk allele carriers will demonstrate a greater reduction in BP with eplerenone and will require a lower dose of eplerenone to reach goal BP as compared with amlodipine.CONCLUSION:
This is a proof-of-concept clinical trial. Positive results support the feasibility of performing genetically-defined, mechanistically-driven trials in HTN. Clinically, it would suggest that genetic biomarkers can identify individuals highly responsive to specific treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pressão Sanguínea
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Proteínas de Ligação a Calmodulina
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Antagonistas de Receptores de Mineralocorticoides
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Eplerenona
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Hipertensão
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Proteínas de Membrana
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article