ClinSeq: A Large-Scale Medical Sequencing Clinical Research Pilot Study

Healthy Volunteers Clinical Trial

Official title: ClinSeq: A Large-Scale Medical Sequencing Clinical Research Pilot Study

Status Active, not recruiting

Clinical Trial Summary

This study will examine genome sequencing in clinical research. Genome sequencing is a process in which researchers analyze (or sequence) part or all of the genome from a single person. The human genome is the material in cells that includes thousands of genes. Gene changes that cause or contribute to disease can be passed on from one generation to the next. This study first focuses on heart disease. Later, researchers hope to study other conditions and genes, with the eventual goal of sequencing most or all of participants genes.

Participants ages 45 to 65 years of age and who do not smoke, may be eligible for this study. Patients will come to the NIH Clinical Research Center for an initial study to last about half a day. They will donate a blood sample and complete a short survey. Then they will meet the genetic counselor to learn more about genome sequencing. Those who join the study will undergo the following procedures and evaluations:

• Family history and medical history.

• Measurement of height and blood pressure.

• Noninvasive heart tests, including electrocardiogram and echocardiogram.

• Drawing of about 3 ounces of blood (5 to 6 tablespoons); part of the blood sample will be used for research and another part for clinical testing.

• Multidetector computed tomography (CT), a test to measure coronary artery calcification, that is, condition of inflexibility.

Each patient will receive a letter with results of the clinical laboratory values and evaluations. There will be recommendations for follow-up with the patient s doctors. Risks in this study include exposure to radiation from the CT test. The radiation amount used is about the same that a person normally receives from natural sources, such as from the sun, outer space, and radioactive materials found naturally in the earth s air and soil. Another slight risk involves reactions to a contrast agent that may be used in the echocardiogram. Side effects can be headache, nausea or vomiting, a warm sensation, and dizziness.

With the samples that patients provide, researchers will start by sequencing about 400 genes related to heart disease. Analysis will take months to complete. Genome sequencing is difficult to do, and researchers have much to learn about the genes they sequence and the gene changes they find. If the researchers find gene changes that are important to the health of a participant, they will contact that participant and give him/her the choice of learning such results.

This study may or may not have a direct benefit for participants. Patients would get free clinical testing for cholesterol, diabetes, and other conditions, as well as information about gene changes. Knowledge gained will benefit people in the future as researchers learn about the relationship between gene changes and health.

Clinical Trial Description

The purpose of ClinSeq is to research large-scale medical sequencing (LSMS) in a clinical research setting. It was developed at a time (approximately 2007) when little was known about the processes and outcomes of doing so. By conducting LSMS and returning individual results to participants, we intended to investigate some of the technical, medical, and genetic counseling issues that accompanied the implementation of LSMS in the clinical setting. Three of our objectives have been met and the relevant findings have largely been published including:

• Developing methods for recruiting and consenting a large, racially-diverse cohort

• Continuing to improve upon existing algorithms for generating and interpreting sequence data

• Build and offer this cohort as a resource for addressing biomedical research questions including investigating the association of genomic variants with traits and phenotypes

However, there is still much to be learned regarding LSMS, much of which is pertinent to our original aim of improving our understanding of socio-behavioral aspects of implementation of LSMS in a clinical research setting. Remaining objectives include:

• To understand patient outcomes (e.g., health behavior, communication, personal utility, emotional) following the receipt of medically actionable results.

• To investigate the impact of an intervention designed to promote better understanding of the

accuracy of genetic sequencing among those consenting to LSMS.

• To investigate the outcomes of returning negative secondary findings reports via a website and compare two versions of a slide developed to improve women s understanding of their residual risk for breast cancer following the receipt of such a report.

• To identify genetic risk factors for diabetes and other metabolic diseases related to glucose metabolism. ;

Related Conditions & MeSH terms

• Atherosclerotic Heart Disease
• Coronary Artery Disease
• Healthy Volunteers
• Heart Diseases
• Myocardial Ischemia

• NCT number: NCT00410241
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Status: Active, not recruiting
• Start date: January 5, 2007