Genetic Epidemiology of Responses to Antihypertensives (GERA)
2013年1月15日 更新者：Stephen T. Turner、Mayo Clinic
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).
研究概览
详细说明
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.
研究类型
观察性的
注册 (实际的)
1200
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Minnesota
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Rochester、Minnesota、美国
- Mayo Clinic
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 60年 (成人)
接受健康志愿者
不
有资格学习的性别
全部
取样方法
非概率样本
研究人群
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.
描述
Primary (essential) hypertension
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 观测模型：队列
- 时间观点：预期
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
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African American hydrochlorothiazide
300 African American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks.
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European American hydrochlorothiazide
300 European American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks
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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
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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
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change in blood pressure
大体时间：4 weeks for hydrochlorothiazide; 6 weeks for candesartan
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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.
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4 weeks for hydrochlorothiazide; 6 weeks for candesartan
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Adverse metabolic changes
大体时间：4 weeks for hydrochlorothiazide only
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Potentially adverse metabolic changes in response to hydrochlorothiazide include changes in fasting serum glucose and insulin; serum potassium; serum lipids (triglycerides, HDL-cholesterol, total cholesterol); and serum uric acid.
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4 weeks for hydrochlorothiazide only
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
赞助
调查人员
- 首席研究员：Stephen T. Turner, M.D.、Mayo Foundation
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Schwartz GL, Turner ST. Pharmacogenetics of antihypertensive drug responses. Am J Pharmacogenomics. 2004;4(3):151-60. doi: 10.2165/00129785-200404030-00002.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
1997年2月1日
初级完成 (实际的)
2008年1月1日
研究完成 (实际的)
2008年1月1日
研究注册日期
首次提交
2000年5月25日
首先提交符合 QC 标准的
2000年5月25日
首次发布 (估计)
2000年5月26日
研究记录更新
最后更新发布 (估计)
2013年1月17日
上次提交的符合 QC 标准的更新
2013年1月15日
最后验证
2013年1月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.