Genetic Analysis of African-Americans With High Blood Pressure
|First Received Date ICMJE||July 18, 2006|
|Last Updated Date||September 26, 2015|
|Start Date ICMJE||October 1999|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00353925 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Genetic Analysis of African-Americans With High Blood Pressure|
|Official Title ICMJE||Genetic Analysis of African-American Hypertensives|
The purpose of this study is to learn if kinase, a protein found in the heart, contributes to thickening of the heart muscle in people with high blood pressure.
A protein called myosin causes the heart to contract and relax. It is thought that kinase changes myosin to make it work better at different heart rates. This study will try to determine if, in some people with high blood pressure, the different forms of this protein cause changes in the heart. If the protein affects the size of the heart, it might be possible to use it to improve heart function after an injury, such as a heart attack.
African-Americans with high blood pressure will be eligible for this study. Current data show that of almost 900 multi-ethnic individuals, the particular form of kinase under study in this project is found exclusively in the African-American population. Study participants will have two tubes of blood drawn for DNA testing to determine what form of kinase is present. An electrocardiogram will also be done if a recent one is not available. Some people may also have an echocardiogram, an ultrasound test to image the heart.
Genetic and in vitro mechanical studies in our laboratory have suggested that the perturbations in the phosphorylation of the cardiac myosin regulatory light chain (RLC) can modulate cardiac function and produce a compensatory hypertrophic response. We have cloned a novel human cardiac kinase (MLCK) that targets the cardiac RLC and identified a common allele unique to the African-American population. The purpose of this protocol is to evaluate a large group of African-American individuals with hypertension and/or cardiac disease, a portion of who will possess this allele. It is well documented that hypertensive African-Americans have an increased prevalence of left ventricular hypertrophy (LVH). We expect that, in this population of hypertensive individuals, we will find an increased left ventricular mass in individuals who are heterozygous or homozygous for this kinase allele.
In this study, patients with the allele can be matched to others in the cohort without the allele and evaluated by echocardiography and cardiac MRI to evaluate cardiac function and chamber size. In addition, metabolic stress testing will be performed to assess the implications of this allele on clinical performance. Another group of 75 Afro-Americans with dilated cardiomyopathy will be referred from local heart failure clinics and evaluated in a similar fashion. Allele prevalence and associated cardiac findings will also be compared with hypertensive patients matched for age and gender. In a parallel experiment, mice over-expressing this kinase, are being generated and will provide us with tissue samples with which to pursue the biophysical basis of the mechanical changes in muscle function.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
|Publications *||Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978 Dec;58(6):1072-83.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Completion Date||December 2007|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Inclusion Criteria (Main Cohort):
Afro-American patients with a history of hypertension
Age greater than or equal to 21 years old
Presence of the kinase allele (homo or heterozygous)
Ability to give informed consent.
Inclusion Criteria (Myopathy Cohort):
All of the above as well as:
Left ventricular ejection fraction of less than 35% by any imaging technique.
For subjects with Kinase Allele:
There will be no exclusion criteria. Patients will be evaluated even if they are only able to participate in part of the study.
For Subjects without the kinase allele and Myopathy Cohort:
History of myocardial infarction
History of significant valve disease
History of primary hyperthropic or infiltrative cardiomyopathy
History of rheumatic heart disease
Chronic atrial arrhythmia, bundle branch block intraventricular conduction defect or definite myocardial infarction on EKG
Inability to perform a metabolic stress test
Inability to perform a cMRI
Poor echocardiographic windows precluding accurate analysis
|Ages||21 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00353925|
|Other Study ID Numbers ICMJE||000003, 00-H-0003|
|Has Data Monitoring Committee||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Heart, Lung, and Blood Institute (NHLBI)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||December 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP