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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. Identifier: NCT00410241
Recruitment Status : Recruiting
First Posted : December 12, 2006
Last Update Posted : November 27, 2020
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Brief 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.

Condition or disease
Healthy Volunteers Atherosclerotic Heart Disease

Detailed Description:

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.

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Study Type : Observational
Estimated Enrollment : 2650 participants
Observational Model: Other
Time Perspective: Prospective
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 have been identified as likely to return for follow up
Family members of Group A1, A2, or A3

Primary Outcome Measures :
  1. Recruit & consent cohort [ Time Frame: 2017 ]
    Developing methods for recruiting and consenting a large, racially-diverse cohort

  2. Improvement to algorithms for interpreting sequence data [ Time Frame: 2023 ]
    Continuing to improve upon existing algorithms for generating and interpreting sequence data

  3. Health behaviors, family communication and understanding [ Time Frame: 2023 ]
    Determining the impacts of LSMS results on health behaviors, familycommunication and understanding

  4. Efficiency of result disclosure [ Time Frame: 2023 ]
    Piloting increasingly efficient models for returning LSMS results

  5. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   6 Years to 95 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Participants in Groups A1, A2, and A3 must reside in the local area or be willing to return up to once per year at their own expense and be the age of 45-65 (or 18-65 for A3) unless they have a significant personal/family history of coronary artery disease, in which case we also accept individuals age 35-65. Participants in Group B will be invited to the study by the team and must be family members of Group A1, A2, or A3 participants.

Group A

We plan to recruit a cohort whose risk to develop coronary artery disease will range from less than 5 percent, based on the 10-year-risk provided by the Framingham risk score, to greater than 10 percent, and including those with known coronary artery disease. The 10-year-risk will be measured by the Framingham risk score based on LDL cholesterol levels.

Individuals eligible for Bins 1-3 of this study will be 45 to 65 years of age, and individuals eligible for Bin 4 must be 35-65 years of age. We selected this cutoff as we are interested in recruiting a cohort whose coronary artery calcification (CAC) measurements range from normal to diseased, and it has been shown that abnormal CAC is infrequent below this age. Also, individuals eligible for this study will be required to have a primary care physician or equivalent with whom we can communicate in the event we uncover a condition that merits follow-up. The exception to this includes individuals in Group A2 who are recruited through the community outreach being done by Ms. Sandra Epps. These individuals will not be required to have a primary care physician, although we will strongly recommend that they attend a community health clinic for follow-up on clinical recommendations from the study. Additionally, individuals eligible for this study will be required to be non-smokers at the time of enrollment, for our purposes defined as someone who has not smoked regularly during the previous 12 months.

Due to the large number of individuals to be recruited and the intention to follow this cohort longitudinally, we will focus our efforts on the metropolitan DC and Baltimore areas (in order to minimize reluctance to participate because of travel limitations). If recruitment is below anticipated levels, we may seek additional subjects from the Richmond, VA metropolitan area. Individuals who are not local to these areas may be considered for participation if they are part of other protocols within NHLBI, and travel to the NIH Clinical Research Center on a regular basis for follow-up, or if they are willing to travel to the NIH as needed for protocol participation (at their own expense). Bin 4 participants will be eligible to have the cost of their transportation, meals and lodging covered if they must travel >500 miles for their clinical visits.

An eligibility screen will be performed by telephone to ascertain age, basic demographics, smoking history, and presence or absence of known cardiovascular disease. We intend to recruit persons of both sexes, of diverse ethnic and racial categories, and from various socio-economic backgrounds.

Group B

The eligibility for Group B is distinct from Group A. Group B eligibility requires:

  1. relative enrolled in Group A
  2. age over 18 years, unless the phenotype under study affects children


Individual excluded from participating in the study include: (1) first-degree relatives of enrolled ClinSeq participants (unless they fall into Group B); and (2) individuals who are directly involved with gathering data and analyzing the clinical and genotyping data, including the Principal Investigator, the Associate Investigators, the ClinSeq staff involved with the subjects at the clinical level (such as the Nurse Practitioner, Genetic counselor, etc.), and the staff at NISC involved with generating and analyzing the sequence data ; and (3) individuals who request access to their raw sequence data for analysis outside of ClinSeq ; and (4) individuals who are already enrolled in another study that provides genome or exome sequencing, such as the GENE-FORECAST Study (14-HG-0048).

Information from the National Library of Medicine

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 identifier (NCT number): NCT00410241

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Contact: Katie L Lewis (301) 594-3063
Contact: Leslie G Biesecker, M.D. (301) 402-2041

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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   
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
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Principal Investigator: Leslie G Biesecker, M.D. National Human Genome Research Institute (NHGRI)
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: National Human Genome Research Institute (NHGRI) Identifier: NCT00410241    
Other Study ID Numbers: 070002
First Posted: December 12, 2006    Key Record Dates
Last Update Posted: November 27, 2020
Last Verified: October 27, 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):
Additional relevant MeSH terms:
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Heart Diseases
Coronary Artery Disease
Myocardial Ischemia
Cardiovascular Diseases
Coronary Disease
Arterial Occlusive Diseases
Vascular Diseases