NCT00005520

Brief Summary

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,200

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Feb 1997

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 1997

Completed
3.3 years until next milestone

First Submitted

Initial submission to the registry

May 25, 2000

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 26, 2000

Completed
7.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2008

Completed
Last Updated

January 17, 2013

Status Verified

January 1, 2013

Enrollment Period

10.9 years

First QC Date

May 25, 2000

Last Update Submit

January 15, 2013

Conditions

Cardiovascular DiseasesHeart DiseasesHypertension

Keywords

HypertensionPharmacogeneticsHydrochlorothiazideCandesartan

Outcome Measures

Primary Outcomes (1)

  • Change in blood pressure

    The blood pressure response to antihypertensive drug therapy was defined by the difference between blood pressure levels prior to and at the end of drug therapy.

    4 weeks for hydrochlorothiazide; 6 weeks for candesartan

Secondary Outcomes (1)

  • Adverse metabolic changes

    4 weeks for hydrochlorothiazide only

Study Arms (4)

African American hydrochlorothiazide

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

Drug: Hydrochlorothiazide

European American hydrochlorothiazide

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

Drug: Hydrochlorothiazide

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

Drug: Candesartan

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

Drug: Candesartan

Interventions

HydrochlorothiazideDRUG
African American hydrochlorothiazideEuropean American hydrochlorothiazide
CandesartanDRUG
African American candesartanEuropean American candesartan

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Adult African American men and women with previously diagnosed primary hypertension were recruited from Atlanta, Georgia; and adult European American man and women with previously diagnosed primary hypertension were recruited from Rochester, Minnesota.

Primary (essential) hypertension

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, United States

Location

Related Publications (19)

  • 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.

    PMID: 11230366BACKGROUND

  • 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.

    PMID: 11080130BACKGROUND

  • 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.

    PMID: 11204288BACKGROUND

  • 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.

    PMID: 11560297BACKGROUND

  • 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.

    PMID: 11551376BACKGROUND

  • 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.

    PMID: 12406976BACKGROUND

  • 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.

    PMID: 12527744BACKGROUND

  • 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.

    PMID: 12517286BACKGROUND

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

    PMID: 15174896BACKGROUND

  • 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.

    PMID: 14735111BACKGROUND

  • 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.

    PMID: 14553962BACKGROUND

  • 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.

    PMID: 15797660BACKGROUND

  • 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.

    PMID: 15683583BACKGROUND

  • 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.

    PMID: 15681560BACKGROUND

  • 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.

    PMID: 15864129BACKGROUND

  • 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.

    PMID: 22413836RESULT

  • 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.

    PMID: 38353215DERIVED

  • 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.

    PMID: 30753254DERIVED

  • 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.

    PMID: 22440088DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, buffy coat, urine.

MeSH Terms

Conditions

Cardiovascular DiseasesHeart DiseasesHypertension

Interventions

Hydrochlorothiazidecandesartan

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

ChlorothiazideBenzothiadiazinesSulfonamidesSulfonesSulfur CompoundsOrganic ChemicalsThiazidesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Stephen T. Turner, M.D.

    Mayo Foundation

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

May 25, 2000

First Posted

May 26, 2000

Study Start

February 1, 1997

Primary Completion

January 1, 2008

Study Completion

January 1, 2008

Last Updated

January 17, 2013

Record last verified: 2013-01

Locations

US(1)