NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing

Cancer Clinical Trial

— NCGENES  

Official title:

NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01969370
• Other study ID #: 11-1865
• Secondary ID: U01HG006487
• Status: Completed
• Phase: N/A
• First received: October 16, 2013
• Last updated: May 2, 2017
• Start date: August 2012
• Est. completion date: March 1, 2017

Study information

• Verified date: May 2017
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is part of a larger consortium project investigating the validity and best use of next-generation sequencing (in particular, whole exome sequencing, or WES) in clinical care. This sub-project is investigating benefits and harms of providing WES diagnostic and different types of incidental findings to adult patients and parents of pediatric patients who undergo WES because they have symptoms suggesting genetic disease.

Description:

This study is part of a larger consortium project investigating the validity and best use of next-generation sequencing (in particular, whole exome sequencing, or WES) in clinical care. Participants are patients who were either seen in the University of North Carolina Cancer and Adult Genetics Clinic or referred to the study by their physician. They will be approached by their physician or a genetic counselor for recruitment. Once enrolled, a clinical geneticist or genetic counselor will obtain consent and collect blood samples to be analyzed using WES. Results may include information related to a diagnosis and incidental information. Medically actionable incidental findings will be CLIA (Clinical Laboratory Improvement Amendments)-certified and returned to participants in a routine genetic counseling session, along with diagnostic findings. Eligible adult participants will be randomized to have the opportunity to choose to get certain types of non-medically actionable incidental findings, as well. Their decisions will be investigated, as will psychosocial and behavioral responses to sequencing and receiving sequencing information. This is a longitudinal, mixed methods study (i.e., multiple assessments pre- and post-return of results, with both quantitative and qualitative methods used to gather data). Because only the quantitative component of the study uses randomization, only measures and procedures associated with that component are described here.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 645
• Est. completion date: March 1, 2017
• Est. primary completion date: March 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

• To receive whole exome sequencing in the study, adult or child patients must have a significant chance of having a genetic disorder, as determined by experts on the study team using criteria that depend on the genetic disorder in question. Representative criteria are listed below and will be considered together to determine whether patterns indicate a likely genetic etiology.

Cancer

• Age of diagnosis

• Presence of bilateral (or multiple) cancers

• Diagnosis of a rare type of cancer

• Details of the family history

Cardiovascular Conditions

• Certain clinical findings, such as prolonged QT interval on electrocardiogram.

• Presence of hypertrophic cardiomyopathy or aortic aneurysm

• Age of diagnosis

• Presence of family history

Pediatric neurodevelopmental disorders

• Specific brain structural brain abnormalities

• Presence of certain seizure types

• Dysmorphic features

Related Conditions & MeSH terms

• Cancer
• Cardiovascular Disease
• Cardiovascular Diseases
• Congenital Abnormalities
• Deafness
• Hearing Loss
• Neurologic Dysfunction
• Neurologic Manifestations

Intervention

Behavioral:
• Experimental
Option to request non-medically actionable incidental information (after receiving education about them)

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Human Genome Research Institute (NHGRI), UNC Lineberger Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Extent of test-specific distress 2 weeks after return of results	Measured with an adapted version of the multidimensional impact of testing scale (MICRA)	2 weeks after return of diagnostic results; for adult patient participants who are eligible and who request them, 2 weeks after return of non-medically actionable incidental results
Secondary	Change in test-specific distress at 3 and 6 months after return of results	Measure is an adapted version of the multidimensional impact of testing scale MICRA)	Adult patient participants: change from 2 weeks after return of diagnostic results to 3 months and 6 months after return of diagnostic results
Secondary	Extent of communication of test results with other people	Motivations of communications will also be assessed and examined for descriptive analyses.	2 weeks after return of diagnostic results
Secondary	Extent of information seeking	Participants will answer questions about the extent to which they sought information about whole exome sequencing and results it produces. Questions also ask about sources of that information (e.g., the Internet, doctors) to provide descriptive data about how participants get information.	2 weeks after consent (T1) and change from T1 to 2 weeks after return of diagnostic results
Secondary	Extent of Decision Regret 2 weeks after consent		All participants: 2 wks after consent (T1)
Secondary	Extent of Decision Regret 2 weeks after return of results	Also administered 2 wks after return of non-medically actionable incidental results for eligible adult patient participants who request them.	All participants: 2 wks after return of diagnostic (dx) results and, for eligible adults who request them, return of incidental results
Secondary	Change in decision regret		For all participants: Change from post-consent to post-return of results; Additional for adults: change at 3 and 6 months after return of dx results
Secondary	Extent of Healthcare Utilization 2 weeks after consent		All participants: 2 wks after consent (T1)
Secondary	Extent of Healthcare Utilization 2 weeks after return of results		All participants: 22 wks after return of diagnostic (dx) results
Secondary	Change in Healthcare Utilization		All participants: Change in utilization from post-consent to post-return of results; Additional for adult patients: Change at 3 and 6 months after return of dx results
Secondary	Enactment of health-related lifestyle behaviors 2 weeks after consent	Behaviors include those related to diet, physical activity, smoking, drinking, and substance use.	Adult participants: 2 wks after consent (T1)
Secondary	Enactment of health-related lifestyle behaviors 2 weeks after return of results	Behaviors include those related to diet, physical activity, smoking, drinking, and substance use.	Adult participants: 2 wks after return of diagnostic (dx) results
Secondary	Change in enactment of health-related lifestyle behaviors	Behaviors include those related to diet, physical activity, smoking, drinking, and substance use.	Adult participants: Change in behaviors from 2 wks after consent (T1) to 2 wks, 3 months, and 6 months after return of dx results
Secondary	Extent of psychological distress 2 weeks after consent	Symptoms of depression and anxiety measured with the Hospital Anxiety and Depression Scale	All participants: 2 wks after consent
Secondary	Extent of psychological distress 2 weeks after return of results	Symptoms of depression and anxiety measured with the Hospital Anxiety and Depression Scale	All participants: 2 wks after return of diagnostic (dx) results
Secondary	Change in extent of psychological distress	Symptoms of depression and anxiety measured with the Hospital Anxiety and Depression Scale	All participants: Change from 2 wks after consent (T1) to 2 wks after return of diagnostic (dx) results; Additional for adult patients: Change at 3 and 6 months after return of dx results
Secondary	Extent of health-related Quality of Life 2 weeks after consent	Measured with the Medical Outcomes Study Short Form-12	All participants: 2 wks after consent (T1)
Secondary	Extent of health-related Quality of Life 2 weeks after return of results	Measured with the Medical Outcomes Study Short Form-12	All participants: 2 wks after return of diagnostic results
Secondary	Change in extent of health-related Quality of Life	Measured with the Medical Outcomes Study Short Form-12	All participants: Change from 2 wks after consent to 2 weeks after return of diagnostic results