Investigating the Feasibility and Implementation of Whole Genome Sequencing in Patients With Suspected Genetic Disorder

NCT03829176 | Completed

• 1 other identifier: 2017P001832
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The study "Investigating the Feasibility and Implementation of Whole Genome Sequencing in Patients With Suspected Genetic Disorder" is a research study that aims to explore the use of whole genome sequencing as a potential first line genetic test for patients for which a genetic diagnosis is suspected. This is an internally funded research study. The investigators will enroll 500 participants who are being seen in one of the various genetics clinics within the Partners HealthCare system for a suspected genetic disorder for which standard-of-care genetic testing is ordered. At the time of their standard-of-care genetic testing, an extra blood sample will be collected, and genome sequencing may be performed. Within 3-4 months, patients learn if they received genome sequencing or not, and any results are returned and explained. Investigators are also studying the experiences of both participants and their providers to better understand how to implement genome sequencing into clinical care.

Conditions

Hereditary Disease; Genetic Predisposition to Disease

Keywords

Whole Genome Sequencing

Outcome Measures

Primary Outcomes (2)

• Diagnostic capabilities: standard-of-care vs whole genome sequencing diagnostic yield

  Assess and compare the overall yields for primary and secondary/incidental findings

  From date of consent until the date of first documented report, assessed up to 12 months

• Diagnostic capabilities: standard-of-care vs whole genome sequencing time to reach diagnosis

  Assess and compare the time that is required to reach a diagnosis by both standard-of-care genetic testing and whole genome sequencing

  From date of consent until the date of first positive report, assessed up to 12 months

Secondary Outcomes (4)

• Resources Needed to Implement WGS at an Academic Medical Center

  Baseline to End of Study, up to 2 years

• Participant characteristics

  Baseline

• Change in perceived utility of genomic results

  Baseline, post-disclosure (approximately 3-4 months after enrollment), 6 months post-disclosure

• Physician confidence and attitudes about genomic sequencing

  Baseline

Study Arms (2)

Standard-of-Care

NO INTERVENTION

Participants who are randomized to not have whole genome sequencing performed on their sample. These participants will have standard-of-care genetic testing only (ordered by their clinical provider) and will not receive genetic results as part of this study.

Whole Genome Sequencing

EXPERIMENTAL

Participants who are randomized to have their genome sequenced and receive a whole genome sequencing report. Results disclosure sessions will include a discussion of the whole genome sequencing report, how the results compare to their standard-of-care genetic testing report, and any potential relevant recommendations. Participants in this arm will receive a copy of their whole genome sequencing report accompanied by a summary letter written by a study genetic counselor.

Genetic: Whole Genome Sequencing

Interventions

Whole Genome Sequencing GENETIC

Participants in this arm will have their sample analyzed by whole genome sequencing (WGS), and a report will be included in their medical record. Analysis will be phenotype-driven (gene list will be curated based on primary indication for testing and other available medical history information), and may include genes on ACMG 59 list if participant elects for these results. This report will include pathogenic, likely pathogenic, and suspicious VUS results identified in the genes analyzed.

Whole Genome Sequencing

Eligibility Criteria

• Age: 3 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants of any gender over the age of 3 months.
• Participants (ages 7+) must be proficient in English. If the participant is under the age of 7 or is over the age of 7 and non-verbal, these criteria apply to their parent who is providing consent.
• Participant is being evaluated clinically at an Partners HealthCare genetics clinic, and not had a prior genetic work up for their referral indication.
• Have a suspected genetic disorder in which the genetic cause is unknown, as confirmed by review of the subject's medical records.
• Genetic testing has been ordered for the participant by their clinical genetics provider as part of a diagnostic workup.
• Willing and able to provide a blood sample. The amount of blood drawn from a patient will be 2 teaspoons or less.
• Ability to provide informed consent or assent to participate in this protocol. Children who have not attained the legal age of consent must provide assent (those who do not have the capacity to assent must not object to taking part), along with permission from the child's parent(s) or guardian. Adults who are unable to consent must be able to provide assent or must not object to taking part, along with permission from their legal authorized representative (LAR).

You may not qualify if:

• Participants who live outside of the United States.
• Non-English-speaking participants.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Broad Institute of MIT and Harvard: collaborator
• Laboratory for Molecular Medicine: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

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MeSH Terms

Conditions

Genetic Diseases, Inborn; Genetic Predisposition to Disease

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Sekar Kathiresan, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Participant, care provider, and study genetic counselor will be blinded to the arm in which the participant was assigned until 3-4 months post-enrollment when the laboratory notifies if a WGS report is generated or not.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Center for Genomic Medicine

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: February 4, 2019
• Study Start: March 1, 2018
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2020
• Last Updated: November 18, 2020

Record last verified: 2020-11

Locations

US (1)