The Genetic Basis of Acquired Heart Disease in Africa

Brief Title

The Genetic Basis of Acquired Heart Disease in Africa

Official Title

The Genetic Basis of Acquired Heart Disease in Africa

Brief Summary

      Background:

      - An acquired heart disease is one that a person gets after they are born. Two of these are
      rheumatic heart disease (RHD) and endomyocardial fibrosis (EMF). They are found more commonly
      in people who live in Africa than in other places in the world. Researchers want to learn
      more about these diseases. They especially want to know what role genes and other factors
      play in them.

      Objective:

      - To identify genetic risk factors for RHD and EMF in sub-Saharan Africa.

      Eligibility:

        -  Children and adults with RHD or EMF.

        -  Healthy volunteers over age 10.

      Design:

        -  Participants will come from existing study groups in Uganda and Nigeria.

        -  Participants may be required to provide a sample of their DNA. They will do this with
           either a blood or saliva sample or a swab of the mouth.

        -  Collected samples will be labeled with a code and sent to a lab in the United States for
           analysis. Remaining portions of participants samples will be stored for an unlimited
           period of time. They may be used in future studies.

        -  Some genetic and health information from participants might be placed into one or more
           scientific databases.

        -  Participant names and identifying information will be kept private. But there is a small
           chance someone could trace them from their genetic information.
    

Detailed Description

      Recent advances in genomic techniques are making possible a new wave of genetic discovery in
      many complex diseases. However, the genetic risk factors for two forms of acquired heart
      disease that are particularly common in Africa - rheumatic heart disease (RHD) and
      endomyocardial fibrosis (EMF) remains unknown. In this application, we propose to evaluate
      genetic risk factors for rheumatic heart disease (RHD) and endomyocardial fibrosis (EMF). A
      number of factors should facilitate the identification of genetic risk variants underlying
      the two conditions. First, both forms of acquired heart disease are endemic to sub-Saharan
      Africa (SSA). Second, affected patients and those who do not develop the conditions share a
      common environment. Finally, the availability of high density SNP arrays to capture common
      and rare variation makes the characterization of genomic variation better than ever. Patients
      will be enrolled at the Uganda Heart Institute in Kampala, Uganda, and at the College of
      Medicine, University of Lagos, Nigeria, with the potential to include other African sites.
      Genomic studies will be done at the NIH.
    


Study Type

Observational


Primary Outcome

Extension of study


Condition

Rheumatic Heart Disease


Study Arms / Comparison Groups

 Control
Description:  Control group

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

736

Start Date

April 3, 2014

Completion Date

February 6, 2020

Primary Completion Date

March 8, 2019

Eligibility Criteria

        -  INCLUSION CRITERIA:

          -  Rheumatic Heart Disease:

        Patients with a definite diagnosis of rheumatic heart disease based on the 2006 World
        Health Organization/National Institutes of Health Joint Criteria
        (http://www.niaid.nih.gov/topics/strepThroat/Documents/groupasequelae.pdf) controls who do
        not meet this criteria. The diagnosis will be made by a cardiologist on our team. The
        method of screening and recruitment will be specific to each of our two sites: Uganda Heart
        Institute and University of Lagos, Nigeria.

        -Uganda Heart Institute:

        --recruitment will be conducted from an existing cohort of patients initially recruited by
        members of our team from 21 randomly selected

        schools in Uganda. Participants meeting the criteria noted above for RHD will be considered
        cases and those who do not will be considered controls. Additionally, parents will be
        invited to participate as controls. For controls, only children over age 10 will be
        considered as this increases the likelihood of exposure

        to S. pyogenes. The initial study was approved by the institutional review boards of the
        Children s National Medical Center (Washington,D.C.), Makerere University (Kampala,
        Uganda), and the

        Ugandan Ministries of Health and Education

          -  University of Lagos:

             --This program will be modeled after the Uganda program. Participants will be screened
             for RHD at the College of Medicine or at randomly selected schools. Participants
             meeting criteria for RHD will be consented as cases and those negative for RHD will be
             consented as controls. Additionally, parents will be invited to participate as
             controls. For controls, only children over age 10 will be considered as this increases
             the likelihood of exposure to S. pyogenes

          -  Endomyocardial Fibrosis (EMF):

               -  Cases: the study will include patients with a diagnosis of EMF based on
                  echocardiography, history, and physical exam performed by cardiologist;on our
                  team Over 50 patients have been identified at the Uganda Heart Institute with EMF
                  and will be contacted for study participation; additionally, newly diagnosed
                  patients at the Uganda Heart Institute will be offered participation.

               -  Controls: Geographic and age matched controls will be used for association study.
                  Controls will be disease free, based on above criteria. We will exclude controls
                  less than 15 years of age based on disease peak around age 10. Controls will be
                  selected from those being screening for RHD

        EXCLUSION CRITERIA:

        -Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of
        their children as minors) or assent.
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Paul S Kruszka, M.D., , 

Location Countries

Nigeria

Location Countries

Nigeria

Administrative Informations


NCT ID

NCT02124109

Organization ID

999914098

Secondary IDs

14-HG-N098

Responsible Party

Sponsor

Study Sponsor

National Human Genome Research Institute (NHGRI)


Study Sponsor

Paul S Kruszka, M.D., Principal Investigator, National Human Genome Research Institute (NHGRI)


Verification Date

February 2020