Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00023556
Status:
COMPLETED
Last Update Posted:
2016-07-12
First Post:
2001-09-07
Brief Title:
Genetic Architecture of Heart Disease in Rural Brazil
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2008-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To examine the genetics of human susceptibility to Chagas disease a leading cause of heart disease throughout Latin America
Detailed Description:
BACKGROUND
Chagas disease is a leading cause of heart disease throughout Latin America affecting between 16 and 18 million individuals The disease named after the Brazilian physician Carlos Chagas who first described it in 1909 exists only on the American Continents It is caused by a flagellate protozoan parasite Trypanosoma cruzi transmitted to humans by blood-sucking triatomine insects known popularly in the different countries as vinchuca barbeiro chipo etc The geographical distribution of the human Tcruzi infection extends from Mexico to the south of Argentina In Brazil alone approximately 10 percent of the population is seropositive for T cruzi Given the large pool of primary hosts for this zoonotic disease complete eradication of Chagas disease through control of the arthropod vector is unlikely Research with humans and animal models indicates that there is variation in susceptibility to infection and disease outcome and that this variation may be due to genetic factors Thus this form of heart disease represents a complex phenotype with potential genetic determinants to both susceptibility to infection and differential disease pathogenesis
DESIGN NARRATIVE
The genetic epidemiology project studies an estimated 1125 Black individuals age 18 years or older from a small community in Posse Brazil in which the study population may be drawn from as few as four to five large pedigrees with varying blood relationships Preliminary pilot data appear very promising regarding the primary hypothesis that specific genetic factors influence the susceptibility to this complex zoonotic disease The investigation will be divided into three parts involving phenotypic characterization statistical genetic analyses to determine the relative proportion of the phenotypic variance due to additive genetic effects and localization of genes influencing the development of Chagas disease
The phenotypic characterization will involve clinical history infection status immunologic studies and cardiac status The chronic phase of T cruzi infection results in Chagas disease manifest as a cardiomyopathy with heart block conduction disturbance ventricular tachyarrhythmia heart failure and sudden arrhythmic death The cardiac phenotyping will involve electrocardiographic time intervals PR interval QRS duration QT interval duration as well as abnormal patterns left anterior fascicular block left ventricular hypertrophy right bundle branch block and possibly some measure of heart failure in terms of New York Heart Association functional classification Right bundle branch block is probably the most frequent early manifestation of chronic cardiac involvement
The genetic linkage studies will attempt to localize genes influencing susceptibility to T cruzi infection ECG parameters eg right bundle branch block and immunologic factors using markers placed approximately every 10 centimorgans cM throughout the genome
About 375 individuals will be sampled per year Each subject will donate two 10 ml samples of blood which will be used for immunoassays for seropositivity for T cruzi and for genotyping with 382 polymorphic short tandem repeats During the initial visits the population subjects will also be interviewed to gather information on demographic pedigree and socioeconomic makeup Additionally questions on pregnancy status household ecology years in the house rooms shared pets rodents food storage triatomid bug history etc and residence history will be determined during the survey In the fourth year the investigators will return to the collection site and administer ECGs on 375 individuals per year
The blood collected in Brazil will be sent to San Antonio for high-throughput genotyping using 382 polymorphic short tandem repeats STRs spread throughout the genome A population specific 10cM map is expected to be useful for linkage analysis
Chagas disease is a leading cause of heart disease throughout Latin America affecting between 16 and 18 million individuals The disease named after the Brazilian physician Carlos Chagas who first described it in 1909 exists only on the American Continents It is caused by a flagellate protozoan parasite Trypanosoma cruzi transmitted to humans by blood-sucking triatomine insects known popularly in the different countries as vinchuca barbeiro chipo etc The geographical distribution of the human Tcruzi infection extends from Mexico to the south of Argentina In Brazil alone approximately 10 percent of the population is seropositive for T cruzi Given the large pool of primary hosts for this zoonotic disease complete eradication of Chagas disease through control of the arthropod vector is unlikely Research with humans and animal models indicates that there is variation in susceptibility to infection and disease outcome and that this variation may be due to genetic factors Thus this form of heart disease represents a complex phenotype with potential genetic determinants to both susceptibility to infection and differential disease pathogenesis
DESIGN NARRATIVE
The genetic epidemiology project studies an estimated 1125 Black individuals age 18 years or older from a small community in Posse Brazil in which the study population may be drawn from as few as four to five large pedigrees with varying blood relationships Preliminary pilot data appear very promising regarding the primary hypothesis that specific genetic factors influence the susceptibility to this complex zoonotic disease The investigation will be divided into three parts involving phenotypic characterization statistical genetic analyses to determine the relative proportion of the phenotypic variance due to additive genetic effects and localization of genes influencing the development of Chagas disease
The phenotypic characterization will involve clinical history infection status immunologic studies and cardiac status The chronic phase of T cruzi infection results in Chagas disease manifest as a cardiomyopathy with heart block conduction disturbance ventricular tachyarrhythmia heart failure and sudden arrhythmic death The cardiac phenotyping will involve electrocardiographic time intervals PR interval QRS duration QT interval duration as well as abnormal patterns left anterior fascicular block left ventricular hypertrophy right bundle branch block and possibly some measure of heart failure in terms of New York Heart Association functional classification Right bundle branch block is probably the most frequent early manifestation of chronic cardiac involvement
The genetic linkage studies will attempt to localize genes influencing susceptibility to T cruzi infection ECG parameters eg right bundle branch block and immunologic factors using markers placed approximately every 10 centimorgans cM throughout the genome
About 375 individuals will be sampled per year Each subject will donate two 10 ml samples of blood which will be used for immunoassays for seropositivity for T cruzi and for genotyping with 382 polymorphic short tandem repeats During the initial visits the population subjects will also be interviewed to gather information on demographic pedigree and socioeconomic makeup Additionally questions on pregnancy status household ecology years in the house rooms shared pets rodents food storage triatomid bug history etc and residence history will be determined during the survey In the fourth year the investigators will return to the collection site and administer ECGs on 375 individuals per year
The blood collected in Brazil will be sent to San Antonio for high-throughput genotyping using 382 polymorphic short tandem repeats STRs spread throughout the genome A population specific 10cM map is expected to be useful for linkage analysis
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL066480-05 | NIH | None | httpsreporternihgovquickSearchR01HL066480-05 |