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

NCT00410241 | Active Not Recruiting

• 2 other identifiers: 07000207-HG-0002
• Study Type: observational
• Target: 1,665
• Locations: 1 country
• Sites: 2

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. ...

Conditions

Healthy Volunteers; Atherosclerotic Heart Disease

Keywords

Genome; Cardiovascular; Volunteers; Genes; Atherosclerosis; Natural History

Outcome Measures

Primary Outcomes (5)

• Recruit & consent cohort

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

  2017

• Offer cohort as resource

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

  2026

• Improvement to algorithms for interpreting sequence data

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

  2026

• Health behavior, family communication and understanding

  Determining the impacts of LSMS results on health behaviors, family communication and understanding

  2026

• Efficiency of result disclosure

  Piloting increasingly efficient models for returning LSMS results

  2026

Study Arms (4)

A1

Self-referred individuals 45-65 at enrollment, 25% of whom had coronary artery disease

A2

Individuals 45-65 at enrollment who self-identified as African, African-American, or Afro-Caribbean

A3

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

B

Family members of Group A1, A2, or A3

Eligibility Criteria

• Age: 6 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants in Groups A reside in the local area or were 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 accepted individuals age 35-65. Participants in Group B were invited to the study by the team and were family members of Group A1, A2, or A3 participants.

You may qualify if:

• Group A

You may not qualify if:

• Criterion #1 (A1): 25% of the participants in this cohort have known coronary artery disease (CAD), which is defined as history of: myocardial infarction, silent myocardial infarction, stent placement, re-vascularization, 50% or more arterial blockage, a calcium
• score greater than the 95th centile based on their age, gender and race (using the MESA calculator at www.mesa-nhlbi.org/Calcium), or a strong family history of CAD along with a personal history of a potentially CAD-related biochemical phenotype, such as elevated
• lipoprotein (a) (Lp(a)).
• Justification: Because CAD was initially the target phenotype under study, it was critical to include a minimal number of participants with documented disease.
• Criterion #2 (A1 \& A2): Individuals eligible for this study are 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 (Wilson et al., 1998).
• Justification: Because our study originally aimed to identify the genetic underpinnings of CAD, we excluded individuals who were smokers because it is a significant, known risk factor for CAD.
• Criterion #3 (A1 and A2): Individuals without CAD must be 45-65 years of age, and individuals with CAD must be 35-65 years of age.
• Justification: We selected our age range based on the manifestations of our target phenotype. We selected the lower limit of this cutoff in order to recruit 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 (Janowitz, Agatston, Kaplan, \& Viamonte, 1993). The lower limit of the age range
• has been expanded in the case of CAD participants to allow for the enrollment of individuals with particularly severe personal or family history of cardiovascular disease. An upper age limit of 65 was chosen to allow for longitudinal study of participants.
• Criterion #4 (A3): Individuals must be 18-65 years of age.
• Justification: As with the A1 and A2 cohort, an upper age limit of 65 was chosen to allow for longitudinal study of participants. However, in contrast to the A1 and A2 cohorts, a lower age limit of 18 was chosen because we are no longer primarily interested in a cardiovascular disease phenotype.
• Criterion #5 (All Cohorts): Subjects must reside in the metropolitan DC and Baltimore areas or travel to the CRC on a regular basis for follow-up, or be willing to travel to the NIH as needed for protocol participation at their own expense (with the exception of some participants with CAD who had extremely compelling personal or family history of disease and we agreed to cover the cost of their transportation, meals and lodging covered for clinical visits because they could not otherwise participate).
• Justification: This criterion is designed to minimize subjects reluctance to participate in ongoing study activities, such as ancillary studies and return to receive genetic testing results.
• Criterion #6: First-degree relatives of enrolled ClinSeq participants are not eligible unless they fall into Group B.
• Justification: These individuals share on average 50% of their genes on autosomal loci, thus possibly reducing the power of a study, such as ClinSeq , with a focus on common diseases.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (2)

Suburban Hospital

Bethesda, Maryland, 20814, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Panganamala RV, Sharma HM, Sprecher H, Geer JC, Cornwell DG. A suggested role for hydrogen peroxide in the biosynthesis of prostaglandins. Prostaglandins. 1974 Oct 10;8(1):3-11. doi: 10.1016/0090-6980(74)90031-8. No abstract available.

  PMID: 4457956 BACKGROUND

• Freed ED, Miller A. An analysis of a continuing medical education questionnaire sent to psychiatrists in the Southern Transvaal. S Afr Med J. 1979 Aug 4;56(5):177-80.

  PMID: 45060 BACKGROUND

• Huggenvik JI, Craven CM, Idzerda RL, Bernstein S, Kaplan J, McKnight GS. A splicing defect in the mouse transferrin gene leads to congenital atransferrinemia. Blood. 1989 Jul;74(1):482-6.

  PMID: 2752125 BACKGROUND

• Chan PA, Lewis KL, Biesecker BB, Erby LH, Fasaye GA, Epps S, Biesecker LG, Turbitt E. Preferences for and acceptability of receiving pharmacogenomic results by mail: A focus group study with a primarily African-American cohort. J Genet Couns. 2021 Dec;30(6):1582-1590. doi: 10.1002/jgc4.1424. Epub 2021 Apr 19.

  PMID: 33876469 DERIVED

• Biesecker BB, Lewis KL, Umstead KL, Johnston JJ, Turbitt E, Fishler KP, Patton JH, Miller IM, Heidlebaugh AR, Biesecker LG. Web Platform vs In-Person Genetic Counselor for Return of Carrier Results From Exome Sequencing: A Randomized Clinical Trial. JAMA Intern Med. 2018 Mar 1;178(3):338-346. doi: 10.1001/jamainternmed.2017.8049.

  PMID: 29356820 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Coronary Artery Disease; Atherosclerosis

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Leslie G Biesecker, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2006
• First Posted: December 12, 2006
• Study Start: January 5, 2007
• Last Updated: May 4, 2026

Record last verified: 2026-04-30

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data in dbGap is stored per NIH policy. Data in the Reverse Phenotyping Core/TGAC browser will be stored for the remainder of the protocol (18-HG-0129) and the time the study is closed, a proposal to the IRB will be made to keep the data or destroy it.
• Access Criteria: dbGap is a controlled-access database with view-only access to summary-level information and individual-level genotype and sequence data associated with phenotypic features. The Reverse Phenotyping Core/TGAC browser allows researchers to identify particular genotypes or ranges of genotypes, while preserving the privacy of study participants by only displaying aggregate data for one or a limited number of loci in a search. The browser is located on NIH servers and searchable only by investigators in the NIH s intramural research program or external collaborators who have contributed sequence data.

Locations

US (2)