Genetic Epidemiology of Responses to Antihypertensives

NCT ID: NCT00005520

Last Updated: 2013-01-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

1200 participants

Study Classification

OBSERVATIONAL

Study Start Date

1997-02-28

Study Completion Date

2008-01-31

Brief Summary

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To determine whether measured variation in genes coding for components of vasoconstriction and volume regulating systems predict interindividual differences in blood pressure response to therapy with a thiazide diuretic, hydrochlorothiazide, or an angiotensin II receptor blocker, candesartan, in hypertensive African-Americans (N=300 treated with each drug) and in hypertensive European Americans (N=300 treated with each drug).

Detailed Description

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BACKGROUND:

Essential hypertension is a common disorder that contributes to morbidity, mortality, and cost of health care, especially among African-Americans. Although a single-drug therapy is commonly prescribed for treatment of hypertension, blood pressure levels are controlled in some individuals but not in others. The study has the potential to identify genes contributing to the etiology of interindividual differences in blood pressure response to diuretic therapy in African-Americans and European Americans.

DESIGN NARRATIVE:

Hypertensive adults were treated with the diuretic hydrochlorothiazide, 25 mg/day, for four weeks; or with the angiotensin II receptor blocker candesartan, 16 mg/day for 2 weeks followed by 32 mg/day for 4 weeks. Interindividual variations in blood pressure responses and in candidate genes coding for components of systems regulating vasoconstriction and volume were measured. In addition, a panel of 500,000 single nucleotide polymorphisms genome-wide was measured in subsets of the most extreme responders and nonresponders to each drug for genome-wide association of analyses.

Conditions

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Cardiovascular Diseases Heart Diseases Hypertension

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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African American hydrochlorothiazide

300 African American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks.

Hydrochlorothiazide

Intervention Type DRUG

European American hydrochlorothiazide

300 European American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks

Hydrochlorothiazide

Intervention Type DRUG

African American candesartan

300 African American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks

Candesartan

Intervention Type DRUG

European American candesartan

300 European American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks

Candesartan

Intervention Type DRUG

Interventions

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Hydrochlorothiazide

Intervention Type DRUG

Candesartan

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Primary (essential) hypertension
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Stephen T. Turner

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stephen T. Turner, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Foundation

Locations

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Mayo Clinic

Rochester, Minnesota, United States

Site Status

Countries

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United States

References

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Turner ST, Schwartz GL, Chapman AB, Boerwinkle E. C825T polymorphism of the G protein beta(3)-subunit and antihypertensive response to a thiazide diuretic. Hypertension. 2001 Feb;37(2 Pt 2):739-43. doi: 10.1161/01.hyp.37.2.739.

Reference Type BACKGROUND
PMID: 11230366 (View on PubMed)

Turner ST, Boerwinkle E. Genetics of hypertension, target-organ complications, and response to therapy. Circulation. 2000 Nov 14;102(20 Suppl 4):IV40-5. doi: 10.1161/01.cir.102.suppl_4.iv-40. No abstract available.

Reference Type BACKGROUND
PMID: 11080130 (View on PubMed)

Turner ST, Schwartz GL, Chapman AB, Hall WD, Boerwinkle E. Antihypertensive pharmacogenetics: getting the right drug into the right patient. J Hypertens. 2001 Jan;19(1):1-11. doi: 10.1097/00004872-200101000-00001.

Reference Type BACKGROUND
PMID: 11204288 (View on PubMed)

Montori VM, Schwartz GL, Chapman AB, Boerwinkle E, Turner ST. Validity of the aldosterone-renin ratio used to screen for primary aldosteronism. Mayo Clin Proc. 2001 Sep;76(9):877-82. doi: 10.4065/76.9.877.

Reference Type BACKGROUND
PMID: 11560297 (View on PubMed)

Turner ST, Schwartz GL, Chapman AB, Boerwinkle E. Use of gene markers to guide antihypertensive therapy. Curr Hypertens Rep. 2001 Oct;3(5):410-5. doi: 10.1007/s11906-001-0059-x.

Reference Type BACKGROUND
PMID: 11551376 (View on PubMed)

Schwartz GL, Chapman AB, Boerwinkle E, Kisabeth RM, Turner ST. Screening for primary aldosteronism: implications of an increased plasma aldosterone/renin ratio. Clin Chem. 2002 Nov;48(11):1919-23.

Reference Type BACKGROUND
PMID: 12406976 (View on PubMed)

Garovic VD, Joyner MJ, Dietz NM, Boerwinkle E, Turner ST. Beta(2)-adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans. J Physiol. 2003 Jan 15;546(Pt 2):583-9. doi: 10.1113/jphysiol.2002.031138.

Reference Type BACKGROUND
PMID: 12527744 (View on PubMed)

Turner ST, Boerwinkle E. Genetics of blood pressure, hypertensive complications, and antihypertensive drug responses. Pharmacogenomics. 2003 Jan;4(1):53-65. doi: 10.1517/phgs.4.1.53.22587.

Reference Type BACKGROUND
PMID: 12517286 (View on PubMed)

Schwartz GL, Turner ST. Pharmacogenetics of antihypertensive drug responses. Am J Pharmacogenomics. 2004;4(3):151-60. doi: 10.2165/00129785-200404030-00002.

Reference Type BACKGROUND
PMID: 15174896 (View on PubMed)

Frazier L, Turner ST, Schwartz GL, Chapman AB, Boerwinkle E. Multilocus effects of the renin-angiotensin-aldosterone system genes on blood pressure response to a thiazide diuretic. Pharmacogenomics J. 2004;4(1):17-23. doi: 10.1038/sj.tpj.6500215.

Reference Type BACKGROUND
PMID: 14735111 (View on PubMed)

Turner ST, Chapman AB, Schwartz GL, Boerwinkle E. Effects of endothelial nitric oxide synthase, alpha-adducin, and other candidate gene polymorphisms on blood pressure response to hydrochlorothiazide. Am J Hypertens. 2003 Oct;16(10):834-9. doi: 10.1016/s0895-7061(03)01011-2.

Reference Type BACKGROUND
PMID: 14553962 (View on PubMed)

Finkielman JD, Schwartz GL, Chapman AB, Boerwinkle E, Turner ST. Lack of agreement between office and ambulatory blood pressure responses to hydrochlorothiazide. Am J Hypertens. 2005 Mar;18(3):398-402. doi: 10.1016/j.amjhyper.2004.10.021.

Reference Type BACKGROUND
PMID: 15797660 (View on PubMed)

Turner ST, Schwartz GL. Gene markers and antihypertensive therapy. Curr Hypertens Rep. 2005 Feb;7(1):21-30. doi: 10.1007/s11906-005-0051-y.

Reference Type BACKGROUND
PMID: 15683583 (View on PubMed)

Schwartz GL, Turner ST. Screening for primary aldosteronism in essential hypertension: diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity. Clin Chem. 2005 Feb;51(2):386-94. doi: 10.1373/clinchem.2004.041780.

Reference Type BACKGROUND
PMID: 15681560 (View on PubMed)

Maitland-van der Zee AH, Turner ST, Schwartz GL, Chapman AB, Klungel OH, Boerwinkle E. A multilocus approach to the antihypertensive pharmacogenetics of hydrochlorothiazide. Pharmacogenet Genomics. 2005 May;15(5):287-93. doi: 10.1097/01213011-200505000-00003.

Reference Type BACKGROUND
PMID: 15864129 (View on PubMed)

Turner ST, Schwartz GL, Chapman AB, Beitelshees AL, Gums JG, Cooper-Dehoff RM, Boerwinkle E, Johnson JA, Bailey KR. Power to identify a genetic predictor of antihypertensive drug response using different methods to measure blood pressure response. J Transl Med. 2012 Mar 13;10:47. doi: 10.1186/1479-5876-10-47.

Reference Type RESULT
PMID: 22413836 (View on PubMed)

Chekka LMS, Tantawy M, Langaee T, Wang D, Renne R, Chapman AB, Gums JG, Boerwinkle E, Cooper-DeHoff RM, Johnson JA. Circulating microRNA Biomarkers of Thiazide Response in Hypertension. J Am Heart Assoc. 2024 Feb 20;13(4):e032433. doi: 10.1161/JAHA.123.032433. Epub 2024 Feb 14.

Reference Type DERIVED
PMID: 38353215 (View on PubMed)

Mehanna M, Wang Z, Gong Y, McDonough CW, Beitelshees AL, Gums JG, Chapman AB, Schwartz GL, Bailey KR, Johnson JA, Turner ST, Cooper-DeHoff RM. Plasma Renin Activity Is a Predictive Biomarker of Blood Pressure Response in European but not in African Americans With Uncomplicated Hypertension. Am J Hypertens. 2019 Jun 11;32(7):668-675. doi: 10.1093/ajh/hpz022.

Reference Type DERIVED
PMID: 30753254 (View on PubMed)

Duarte JD, Zineh I, Burkley B, Gong Y, Langaee TY, Turner ST, Chapman AB, Boerwinkle E, Gums JG, Cooper-Dehoff RM, Beitelshees AL, Bailey KR, Fillingim RB, Kone BC, Johnson JA. Effects of genetic variation in H3K79 methylation regulatory genes on clinical blood pressure and blood pressure response to hydrochlorothiazide. J Transl Med. 2012 Mar 22;10:56. doi: 10.1186/1479-5876-10-56.

Reference Type DERIVED
PMID: 22440088 (View on PubMed)

Other Identifiers

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R01HL053330

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01HL074735

Identifier Type: NIH

Identifier Source: secondary_id

View Link

05-004017

Identifier Type: -

Identifier Source: org_study_id

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