Genomic Services Research Program

Breast Cancer Clinical Trial

Official title:

Genomic Services Research Program

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02595957
• Other study ID #: 160017
• Secondary ID: 16-HG-0017
• Status: Recruiting
• Start date: September 16, 2014
• Est. completion date: December 31, 2028

Study information

• Verified date: June 12, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Julie Sapp
• Phone: (301) 435-2832
• Email: sappj[@]mail.nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background:

Genes are the instructions a person s body uses to function. Genome sequencing is a new way to look at genes that your main research team is using to learn the causes of the condition they are studying. When a new cause is found this way, it is called a primary variant. Each person has many variants. Most do not cause disease. Sequencing can also find secondary variants. These are not related to the condition your main research team is studying, but may show a person to be at high risk for cancer or another condition. Researchers want to learn more about what it means to have a secondary variant.

Objectives:

To find new gene changes that lead to certain medical conditions. To better understand the causes of certain diseases. To learn about how people understand their genetic test results.

Eligibility:

People with rare diseases who have already consented to and enrolled in another protocol run by a group other than the National Human Genome Research Institute.

Design:

DNA samples that were already collected will be studied.

Participants may be asked to send in a second DNA sample (blood or saliva). These will be used to verify any findings.

If a primary variant for the participant s health condition is found through genome sequencing, this will be shared with the participant by their primary research team.

If the participant has a secondary finding, it will be shared by phone call or videoconference by this research group in the National Human Genome Research Institute. Some participants may get their results in person at the clinic.

Three months after getting their secondary findings, participants will do an online survey and phone interview. They will be asked about how they have used the information.

Some people who do not receive a secondary finding from genome sequencing will be asked to do an online survey three months after they get that result.

Participants who have a secondary finding can get genetic counseling.

Description:

The implementation of genome and exome sequencing creates challenges and opportunities, particularly with respect to the return of medically-actionable secondary findings (SF). This study seeks to investigate the utility and effectiveness of returning SF generated via research or clinical sequencing by studying individuals who have received such findings. Our objectives with this protocol have evolved over time and have been substantially informed by our experiences in returning SF through sequencing initiatives such as the ClinSeq study, the Clinical Center Genomics Opportunity (CCGO), and the Secondary Genomic Findings Service (SGFS). Our work with these studies/initiatives suggests that much remains unknown about how recipients of SF understand these findings, communicate them to their health professionals and families, and whether they adhere to recommended health-preserving actions in both the short and long-term. As well, recipients of SF are an unselected population in which to investigate penetrance of disorders associated with SF genes. Thus, this protocol aims to explore important questions of clinical utility associated with SF return and penetrance of SF-related disorders. Healthcare actions and family communication (clinical utility) are assessed by interviews and surveys with SF recipients. This protocol also includes a pilot program in which selected participants will be invited to the NIH for bespoke phenotyping to uncover the presence of disease and explore avenues to develop interventions to enhance outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 105 Years

Eligibility

• ELIGIBILITY CRITERIA:

• Any English- or Spanish-speaking recipient of a SF. The circumstances under which SF are generated (either clinically or as part of research studies) indicate that these individuals may represent a wide range of ages of patients, children and

adults.

• For minors or decisionally-impaired adults, one parent/guardian, typically the self designated primary health care support parent, will be enrolled. If the parents claim equal roles, whichever of the parents selects to participate in the interview/survey will be enrolled.

• It is important to emphasize that we will not ask minors or decisionally impaired adults to participate in the social and behavioral components of the study. Because validated instruments for our surveys largely do not exist in languages other than English, we cannot administer these measures to non-English speakers.

• We may enroll a child in this protocol if he/she is the only person in his/her family who has the SF, is symptomatic of the disease, or is in the age range to receive screening for the disease (e.g., Wilson disease and familial hypercholesterolemia have childhood onset). We will not enroll neonates (less than one month old).

• We may enroll adults who are unable to consent (i.e., an individual who is impaired at the time of consent) in this protocol if he/she is the only person in his/her family who has the SF, is symptomatic of the disease, or is in the age range to receive screening for the disease.

• We may enroll women who are pregnant in this protocol and women who become pregnant during the study can continue their participation. We will not perform prenatal genetic testing.

• NIH staff members are not prohibited from enrollment if they meet the study s eligibility criteria.

Related Conditions & MeSH terms

• Breast Cancer
• Colon Cancer
• Colonic Neoplasms

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Human Genome Research Institute (NHGRI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Sapp JC, Johnston JJ, Driscoll K, Heidlebaugh AR, Miren Sagardia A, Dogbe DN, Umstead KL, Turbitt E, Alevizos I, Baron J, Bonnemann C, Brooks B, Donkervoort S, Jee YH, Linehan WM, McMahon FJ, Moss J, Mullikin JC, Nielsen D, Pelayo E, Remaley AT, Siegel R, Su H, Zarate C; NISC Comparative Sequencing Program; Manolio TA, Biesecker BB, Biesecker LG. Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot. Am J Hum Genet. 2018 Sep 6;103(3):358-366. doi: 10.1016/j.ajhg.2018.07.018. Epub 2018 Aug 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Responses and perceptions	We will assess affective responses and healthcare and behavioral changes to receiving positive SF results	enrollment and return of results
Primary	Family based positive predictive value	We will assess penetrance using the family-based positive predictive value metric	return of results and cascade testing
Primary	Adherence to medical recommendations	We will assess what individual, community, and systemic factors influence recipients follow through on recommendations and how they communicate SF results with family members.	enrollment and return of results
Primary	Health impacts of SF receipt	We will assess the health impacts of SF receipt and healthcare processes affecting outcomes in SF recipients.	enrollment and return of results

External Links

•   NIH Clinical Center Detailed Web Page