search
Back to results

Genetic Architecture of Heart Disease in Rural Brazil

Primary Purpose

Chagas Disease, Heart Diseases, Arrhythmia

Status
Completed
Phase
Locations
Study Type
Observational
Intervention
Sponsored by
National Heart, Lung, and Blood Institute (NHLBI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an observational trial for Chagas Disease

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

No eligibility criteria

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Secondary Outcome Measures

    Full Information

    First Posted
    September 7, 2001
    Last Updated
    July 11, 2016
    Sponsor
    National Heart, Lung, and Blood Institute (NHLBI)
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00023556
    Brief Title
    Genetic Architecture of Heart Disease in Rural Brazil
    Study Type
    Observational

    2. Study Status

    Record Verification Date
    August 2008
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2001 (undefined)
    Primary Completion Date
    August 2008 (Actual)
    Study Completion Date
    August 2008 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    National Heart, Lung, and Blood Institute (NHLBI)

    4. Oversight

    5. Study Description

    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 T.cruzi 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 1,125 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 (e.g., 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chagas Disease, Heart Diseases, Arrhythmia, Heart Failure, Congestive

    7. Study Design

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    100 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    No eligibility criteria
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Sarah Williams-Blangero
    Organizational Affiliation
    Southwest Foundation for Biomedical Research

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    12700060
    Citation
    Williams-Blangero S, VandeBerg JL, Blangero J, Correa-Oliveira R. Genetic epidemiology of Trypanosoma cruzi infection and Chagas' disease. Front Biosci. 2003 May 1;8:e337-45. doi: 10.2741/1058.
    Results Reference
    background

    Learn more about this trial

    Genetic Architecture of Heart Disease in Rural Brazil

    We'll reach out to this number within 24 hrs