ClinSeq: A Large-Scale Medical Sequencing Clinical Research Pilot Study
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00410241|
Recruitment Status : Recruiting
First Posted : December 12, 2006
Last Update Posted : October 1, 2019
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.
|Condition or disease|
|Healthy Volunteers Atherosclerotic Heart Disease|
The purpose of ClinSeq is to pilot large-scale medical sequencing (LSMS) in a clinical
research setting. By conducting LSMS and returning individual results to participants, we will investigate some of the technical, medical, and genetic counseling issues that accompany the implementation of LSMS in the clinical setting.
A cohort of ~2,000 individuals selected from the surrounding general population is being evaluated at the NIH Clinical Research Center (CRC) for a common set of cardiovascular phenotypic features, including, but not limited to, coronary artery calcification, lipid profiles, and blood pressure. During their initial visit, participants undergo a brief clinical evaluation, and have blood samples collected for genomic analysis. Additionally, they are asked to provide baseline information about pertinent health behavior and a family history. During their initial visit and as the study progresses, participants may be asked to complete surveys related to various socio-behavioral aspects of their participation, such as their attitudes toward learning individual results or health behaviors related to receipt of results.
Most participants have exome sequencing (ES), and selected participants will have genome sequencing (GS). We have developed analytic algorithms to distinguish potentially pathogenic genetic alterations from normal variation (Gonsalves et al., 2013; Johnston et al., 2012; Ng et al., 2013) and will test for associations of genomic variants with a variety of phenotypes. Sequence variants deemed clinically relevant are validated in a CLIA-certified laboratory and the results offered to that subject. ClinSeq is designed to provide the long-term potential for pursuing many different clinical projects.
Relatives of ClinSeq participants may be invited to enroll in the project for more
limited studies if their participation aids our understanding of the gene variants detected in the
probands. For example, these relatives may undergo genetic testing for co-segregation of known or suspected disease-causing variants, and/or phenotyping relevant to the disease in question.
We aim to utilize the procedures and infrastructure we have developed for generating and analyzing data to address some of the logistic,biomedical, and counseling challenges related to LSMS.
|Study Type :||Observational|
|Estimated Enrollment :||2650 participants|
|Official Title:||ClinSeq: A Large-Scale Medical Sequencing Clinical Research Pilot Study|
|Actual Study Start Date :||January 5, 2007|
Self-referred individuals 45-65 at enrollment, 25% of whom had coronary artery disease
Individuals 45-65 at enrollment who self identified as African, African-American or Afro-Caribbean
Adults aged 18-65 at the time of enrollment, including subjects of both sexes, who present to the NIH blood bank for a donation.
Family members of Group A1 or A2 participants
- Recruit & consent cohort [ Time Frame: 2017 ]Developing methods for recruiting and consenting a large, racially-diverse cohort
- Improvement to algorithms for interpreting sequence data [ Time Frame: 2023 ]Continuing to improve upon existing algorithms for generating and interpreting sequence data
- Health behaviors, family communication and understanding [ Time Frame: 2023 ]Determining the impacts of LSMS results on health behaviors, familycommunication and understanding
- Efficiency of result disclosure [ Time Frame: 2023 ]Piloting increasingly efficient models for returning LSMS results
- Offer cohort as resource [ Time Frame: 2023 ]Build and offer this cohort as a resource for addressing biomedical research questions including investigating the association of genomicvariants with traits and phenotypes.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00410241
|Contact: Katie L Lewis||(301) firstname.lastname@example.org|
|Contact: Leslie G Biesecker, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Leslie G Biesecker, M.D.||National Human Genome Research Institute (NHGRI)|