Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Implementation of Carrier Status Using Next Generation Sequencing (NextGen)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01902901
Recruitment Status : Completed
First Posted : July 18, 2013
Results First Posted : March 13, 2019
Last Update Posted : April 17, 2019
Sponsor:
Collaborator:
National Human Genome Research Institute (NHGRI)
Information provided by (Responsible Party):
Kaiser Permanente

Tracking Information
First Submitted Date  ICMJE July 10, 2013
First Posted Date  ICMJE July 18, 2013
Results First Submitted Date  ICMJE June 20, 2018
Results First Posted Date  ICMJE March 13, 2019
Last Update Posted Date April 17, 2019
Actual Study Start Date  ICMJE January 2014
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2019)
Number of Patients That Receive Carrier Testing and Have Results to Return [ Time Frame: Assessed annually for 4 years, data at the end of the study reported. ]
The investigators will record the number of patients that have both single carrier status testing (usual care) and WGS testing and track how many patients have results to return.
Original Primary Outcome Measures  ICMJE
 (submitted: July 16, 2013)
Number of Patients That Receive Carrier Testing and Have Results to Return [ Time Frame: Annually for 4 years ]
The investigators will record the number of patients that have both single carrier status testing (usual care) and WGS testing and track how many patients have results to return.
Change History Complete list of historical versions of study NCT01902901 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2019)
Patient Satisfaction [ Time Frame: Assessed annually for 4 years, data at the end of Year 3 reported. ]
Through surveys, interviews, and observations with patients, the investigators will assess their satisfaction with the testing and return of results process.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2013)
Patient Satisfaction [ Time Frame: Annually for 4 years ]
Through surveys, interviews, and observations with patients, the investigators will assess their satisfaction with the testing and return of results process.
Current Other Pre-specified Outcome Measures
 (submitted: April 8, 2019)
Healthcare Utilization [ Time Frame: The end of Year 4 ]
The investigators will evaluate if expanded carrier testing using WGS causes an increase in subsequent health care utilization compared to usual care (typically just cystic fibrosis carrier testing).
Original Other Pre-specified Outcome Measures
 (submitted: July 16, 2013)
  • Provider satisfaction [ Time Frame: Annually for 4 years ]
    Through interviews and observations with providers, the investigators will assess the participants' satisfaction with the testing and return of results process.
  • Cost-analysis [ Time Frame: Year 4 ]
    The investigators will evaluate the impact of expanded carrier test using WGS on subsequent health care utilization, and compare the cost of delivery of WGS to usual care.
 
Descriptive Information
Brief Title  ICMJE Clinical Implementation of Carrier Status Using Next Generation Sequencing
Official Title  ICMJE Clinical Implementation of Carrier Status Using Next Generation Sequencing
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Condition  ICMJE Genetic Disorders
Intervention  ICMJE
  • Genetic: Whole Genome Sequencing
    Participants will receive Whole Genome Sequencing
  • Genetic: Carrier status testing
    Carrier status testing
Study Arms  ICMJE
  • Active Comparator: Usual care
    Requested carrier status testing.
    Intervention: Genetic: Carrier status testing
  • Experimental: Whole Genome Sequencing
    These participants will receive the carrier status testing they requested from their provider, plus whole genome sequencing.
    Interventions:
    • Genetic: Whole Genome Sequencing
    • Genetic: Carrier status testing
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 1, 2017)
384
Original Estimated Enrollment  ICMJE
 (submitted: July 16, 2013)
400
Actual Study Completion Date  ICMJE May 2018
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01902901
Other Study ID Numbers  ICMJE 1UM1HG007292-01( U.S. NIH Grant/Contract )
1UM1HG007292-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Genome sequencing data is shared with dbGaP, and variants are shared with Clinvar.
Time Frame: Ongoing
Access Criteria: Request to dbGaP
Responsible Party Kaiser Permanente
Study Sponsor  ICMJE Kaiser Permanente
Collaborators  ICMJE National Human Genome Research Institute (NHGRI)
Investigators  ICMJE
Principal Investigator: Katrina Goddard, PhD Kaiser Permanente
Principal Investigator: Benjamin Wilfond, MD Seattle Children's Hospital
PRS Account Kaiser Permanente
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP