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http://purl.uniprot.org/citations/33904521http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33904521http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/33904521http://purl.org/dc/terms/identifier"doi:10.1097/fpc.0000000000000425"xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/author"Williams J.S."xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/author"Adler G.K."xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/author"Williams G.H."xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/author"Green J.A.E.M."xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/author"Hornik E.S."xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/author"Koefoed A.W."xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/author"Stone I.B."xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/name"Pharmacogenet Genomics"xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/pages"83-88"xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/title"Striatin genotype-based, mineralocorticoid receptor antagonist-driven clinical trial: study rationale and design."xsd:string
http://purl.uniprot.org/citations/33904521http://purl.uniprot.org/core/volume"31"xsd:string
http://purl.uniprot.org/citations/33904521http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33904521
http://purl.uniprot.org/citations/33904521http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33904521
http://purl.uniprot.org/uniprot/#_Q3B874-mappedCitation-33904521http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33904521
http://purl.uniprot.org/uniprot/#_O43815-mappedCitation-33904521http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33904521
http://purl.uniprot.org/uniprot/Q3B874http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33904521
http://purl.uniprot.org/uniprot/O43815http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33904521