Clinical Implementation of Carrier Status Using Next Generation Sequencing

NCT ID: NCT01902901

Last Updated: 2019-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 384 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2018-05-31

Brief Summary

This study is conducting a randomized controlled trial (RCT) with up to 400 subjects (women & partners) seeking pre-conception carrier testing to assess the impact of the program using Whole Genome Sequencing (WGS).

1. The investigators hypothesize that whole genome sequencing will increase the detection of carrier status for Mendelian recessive and x-linked conditions.

2. The investigators hypothesize that parents will act on the knowledge of their carrier status by making different reproductive choices than parents who do not receive this information.

3. The investigators hypothesize that the psychosocial risks are increased among parents who receive expanded carrier screening using Next Generation Sequencing (NGS) compared with usual care.

Detailed Description

Project 1-Clinical Intervention and Outcomes Aim 1: To conduct a randomized controlled trial (RCT) with up to 400 subjects (women & partners) seeking pre-conception carrier testing to assess the impact of the program using Whole Genome Sequencing (WGS).

Aim 2: To develop processes for delivering information from WGS directly into the patient's electronic medical record, and establish innovative reporting strategies that are informative for clinicians and couples acting on this information.

Aim 3: To measure for the integration of sequence information in clinical care for both carrier status and secondary findings including:

1. Patient reported outcomes (PRO) on the impact on quality of life, satisfaction with care, timeliness of reporting, and use of the genomic information.

2. Process outcomes such as timeliness, number of reportable findings, and time of interpretation.

Project 2 -WGS technology, informatics, and Return of Results Committee (RORC)

Aim 1: To generate whole genome sequence and interpret variants on samples randomized from the Kaiser Permanente Northwest (KPNW) preconception carrier screening cohort.

1. To perform whole genome sequencing, assembly, and variant detection for each sample.

2. To provide variant data on each sample with annotation and ranking of clinical significance.

3. To validate data using an orthogonal platform for findings relevant to carrier status and actionable secondary findings.

Aim 2: To develop and implement a return of results committee (RORC) that incorporates evidence to assess criteria for reporting carrier status for reproductive decision making and secondary findings.

Project 3 - Ethical and Psychosocial Implications

Aim 1: To evaluate, patient and clinical perspectives on informational needs, satisfaction, knowledge, and decision-making relating to the choice to obtain results of carrier status from WGS in four categories of genetic conditions.

Aim 2: To evaluate, from patient and clinician perspectives, the immediate and downstream ethical, psychosocial, and behavioral consequences of expanded carrier screening using WGS.

Aim 3: To evaluate the impact of expanded carrier test using WGS on subsequent health care utilization, and to compare the cost of delivery WGS to usual care.

Conditions

Genetic Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Usual care

Requested carrier status testing.

Group Type: ACTIVE_COMPARATOR

Carrier status testing

Intervention Type: GENETIC

Carrier status testing

Whole Genome Sequencing

These participants will receive the carrier status testing they requested from their provider, plus whole genome sequencing.

Group Type: EXPERIMENTAL

Whole Genome Sequencing

Intervention Type: GENETIC

Participants will receive Whole Genome Sequencing

Carrier status testing

Intervention Type: GENETIC

Carrier status testing

Interventions

Whole Genome Sequencing

Participants will receive Whole Genome Sequencing

Intervention Type: GENETIC

Carrier status testing

Carrier status testing

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Seeking pre-conception carrier status testing or had carrier testing during pregnancy
• Women with a male partner that can be contacted
• Kaiser Permanente Northwest members
• English speaking
• Not currently pregnant

Exclusion Criteria

• Currently pregnant
• No known or accessible male partner
• Not an English speaker
• Not a Kaiser Permanente member

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Human Genome Research Institute (NHGRI)

NIH

Sponsor Role: collaborator

Kaiser Permanente

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Katrina Goddard, PhD

Role: PRINCIPAL_INVESTIGATOR

Kaiser Permanente

Benjamin Wilfond, MD

Role: PRINCIPAL_INVESTIGATOR

Seattle Children's Hospital

Locations

Kaiser Permanente Northwest

Portland, Oregon, United States

Countries

United States

Other Identifiers

1UM1HG007292-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UM1HG007292-01

Identifier Type: NIH

Identifier Source: org_study_id

View Link