Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT01316783 |
| Other study ID # |
110110 |
| Secondary ID |
11-HG-0110 |
| Status |
Enrolling by invitation |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 6, 2011 |
Study information
| Verified date |
February 23, 2024 |
| Source |
National Institutes of Health Clinical Center (CC) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background:
- African Americans have one of the highest rates of type 2 diabetes in the United States,
and often have other medical problems related to obesity and cardiovascular disease. These
conditions have various risk factors, including high blood sugar levels, high cholesterol
levels, and insulin resistance. However, these risk factors have not been studied very
closely in individuals with African ancestry, including Afro-Caribbean and sub-Saharan Africa
migrant populations. Researchers are interested in conducting a genetic study on obesity,
adult-onset diabetes, heart disease, and other common health conditions in individuals with
African ancestry.
Objectives:
- To collect genetic and non-genetic information from individuals with African ancestry to
study common health conditions related to obesity, adult-onset diabetes, and heart disease.
Eligibility:
- Individuals at least 18 years of age who self-identify as African American, Afro-Caribbean,
or migrants from sub Saharan Africa.
Design:
- Participants will undergo a physical examination and will provide a blood sample for
study.
- Participants will also answer questions about personal and family medical history and
current lifestyle behaviors.
- No treatment will be provided as part of this protocol.
Description:
Study Design:
The study is comprised of a population-based sample from Dr. Anne Sumner s ongoing NIDDK
studies to perform a quantitative trait analysis of multiple metabolic biomarkers and
disorders including T2D, hypertension, CVD and obesity in a total of 1000 people of African
ancestry and approximately100 whites (who will serve as a comparison group) residing in the
United States. Because some of the identified variants will be rare, we will use the methods
proposed by Li and Leal. Under an additive model and at a MAF of 0.04, this sample size has
80% power to detect a genetic effect that may explain a 1-4 unit change depending on the
trait in question (e.g., BMI in kg/m^2, blood glucose in mg/dL, systolic and diastolic BP in
mmHG).
We will also perform exome sequencing of 48 cases of African descent and genotype identified
variants in the larger cohort. Cases for exome sequencing will consist of individuals who
have more than one metabolic condition, i.e., diabetes, pre-diabetes, obesity, hypertension
and/or dyslipidemia. We propose to carry out exome capture of 48 individuals (96
chromosomes). Given the probability of observing a specific allele one or more times of 1 -
(1-p)^2N (where p is the minor allele frequency), a sample of 48 individuals (96 chromosomes)
provides a 99% probability of finding a sequence variant with a minor allele frequency (MAF)
of 0.05, 98% probability of finding a variant with an MAF of 0.04, 95% probability of finding
a variant with an MAF of 0.03, 86% probability of finding a variant with an MAF of 0.02 and
62% probability of finding a variant with an MAF of 0.01. We will use four main filters to
identify potential variants with functional consequences. We will look for 1) SNPs that are
intragenic or in promoter regions, 2) SNPs that cause nonsynonymous coding changes according
to Polyphen and SIFT, 3) nonsense mutations, and 4) missense mutations that have possible or
probable damaging protein effects. All selected SNPs will be tested for potential association
with all metabolic parameters in this study.
Primary Objective:
Genotype variants of interest from genetic epidemiology studies conducted in Dr. Rotimi s lab
in these individuals, with thorough clinical measurements available, in order to investigate
biological mechanisms underlying observed associations.
Secondary Objectives:
Conduct whole-exome capture on a subset of cases with at least 2 metabolic disorders (i.e.,
diabetes, pre-diabetes, obesity, hypertension and/or dyslipidemia). Genotype identified
variants in the larger cohort of 1000 persons or in existing studies of African ancestry
individuals (Howard University Family Study or Africa America Diabetes Mellitus Study).
Exploratory Objectives:
Endpoints: Obesity, Metabolic Syndrome, Dyslipidemia, Pre-Diabetes, and Diabetes
