Clinical trial NCT01969370: NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing
Official title: NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer
Cardiovascular Disease
Neurologic Dysfunction
Congenital Abnormalities
Hearing Loss
Keywords: Cancer
Cardiovascular disease
Neurodegenerative disease
Neurodevelopmental disease
Dysmorphology
Hearing loss
Other conditions, including ophthalmic conditions
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Human Genome Research Institute (NHGRI)
name: UNC Lineberger Comprehensive Cancer Center
First posted: 2013-10-25
Enrollment: 645
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: - 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

Primary outcomes:
measure: Extent of test-specific distress 2 weeks after return of results
timeFrame: 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 outcomes:
measure: Change in test-specific distress at 3 and 6 months after return of results
timeFrame: Adult patient participants: change from 2 weeks after return of diagnostic results to 3 months and 6 months after return of diagnostic results
measure: Extent of communication of test results with other people
timeFrame: 2 weeks after return of diagnostic results
measure: Extent of information seeking
timeFrame: 2 weeks after consent (T1) and change from T1 to 2 weeks after return of diagnostic results
measure: Extent of Decision Regret 2 weeks after consent
timeFrame: All participants: 2 wks after consent (T1)
measure: Extent of Decision Regret 2 weeks after return of results
timeFrame: All participants: 2 wks after return of diagnostic (dx) results and, for eligible adults who request them, return of incidental results
measure: Change in decision regret
timeFrame: 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
measure: Extent of Healthcare Utilization 2 weeks after consent
timeFrame: All participants: 2 wks after consent (T1)
measure: Extent of Healthcare Utilization 2 weeks after return of results
timeFrame: All participants: 22 wks after return of diagnostic (dx) results
measure: Change in Healthcare Utilization
timeFrame: 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
measure: Enactment of health-related lifestyle behaviors 2 weeks after consent
timeFrame: Adult participants: 2 wks after consent (T1)
measure: Enactment of health-related lifestyle behaviors 2 weeks after return of results
timeFrame: Adult participants: 2 wks after return of diagnostic (dx) results
measure: Change in enactment of health-related lifestyle behaviors
timeFrame: Adult participants: Change in behaviors from 2 wks after consent (T1) to 2 wks, 3 months, and 6 months after return of dx results
measure: Extent of psychological distress 2 weeks after consent
timeFrame: All participants: 2 wks after consent
measure: Extent of psychological distress 2 weeks after return of results
timeFrame: All participants: 2 wks after return of diagnostic (dx) results
measure: Change in extent of psychological distress
timeFrame: 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
measure: Extent of health-related Quality of Life 2 weeks after consent
timeFrame: All participants: 2 wks after consent (T1)
measure: Extent of health-related Quality of Life 2 weeks after return of results
timeFrame: All participants: 2 wks after return of diagnostic results
measure: Change in extent of health-related Quality of Life
timeFrame: All participants: Change from 2 wks after consent to 2 weeks after return of diagnostic results
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: James P Evans, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina
name: Gail Henderson, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina
name: Jonathan S Berg, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina
name: Christine Rini, Ph.D
role: STUDY_DIRECTOR
References:
citation: Rini C, Roche MI, Lin FC, Foreman AKM, Khan CM, Griesemer I, Waltz M, Lee K, O'Daniel JM, Evans JP, Berg JS, Henderson GE. Burden or benefit? Effects of providing education about and the option to request additional genomic findings from diagnostic exome sequencing: A randomized controlled trial. Patient Educ Couns. 2021 Dec;104(12):2989-2998. doi: 10.1016/j.pec.2021.04.026. Epub 2021 Apr 29.