NeuroSeq: A Prospective Trial to Evaluate the Diagnostic Yield of Whole Genome Sequencing (WGS) in Adult Neurology (NeuroSEQ)

NeuroSeq: A Prospective Trial to Evaluate the Diagnostic Yield of Human Whole Genome Sequencing (WGS) Compared to Standard of Care in Adults With Suspected Genetic Neurological Disorders

Prospective, multi-site, single-arm study to evaluate the diagnostic yield of cWGS in adults with neurological disorders. A single cohort naive of genetic testing will receive standard of care testing for 180 days followed by cWGS. The cohort will be followed for a total of 365 days following enrollment.

Study Overview

• Status: Completed
• Conditions: Neurologic Disorder; Neurologic Deficits; Neurologic Abnormalities
• Intervention / Treatment: Other: clinical Whole Genome Sequencing

Detailed Description

This is a prospective, randomized study to evaluate the diagnostic yield of SOC compared to cWGS in each participant. Throughout this study, each participant will receive SOC testing as determined by the site clinical team. After the physician orders SOC testing during standard clinical practice, the subject will be introduced and invited to participate in the study. On Day 180, the participant will receive a cWGS result and the participant will continue to be followed for an additional 180 days. A blood sample from each enrolled participant will be collected and shipped to the Illumina Clinical Services Laboratory ("ICSL"), which is Clinical Laboratory Improvement Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited. ICSL will conduct cWGS testing with the TruGenome Undiagnosed Disease Test ("TruGenome Test"). The TruGenome Test cWGS results will be provided to the Principal Investigator (PI) or designee who will evaluate each participant's test outcome based on aggregate medical information.

• Study Type: Observational
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univ. of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

A single cohort presenting with phenotypic symptoms of a suspected genetic neurological disorder who have been scheduled for Standard of Care (SOC) molecular testing as determined by their physician.

Description

Inclusion Criteria:

1. Age ≥ 18 years at the time of consent
2. Participant is referred to a Neurogenetics Program due to suspected genetic etiology of a neurological syndrome
3. No history of prior genetic testing for the suspected condition in the participant or any family member with a similar phenotype
4. Must be able to have one - 4 to 6 ml tube of whole blood drawn for testing
5. Able to provide written consent. If participant unable to do so, a legally authorized representative (LAR) must do so on behalf of the participant

Exclusion Criteria:

1. Any known non-genetic cause(s) of disease, disorder, or phenotypic defect
2. Eligibility for enrollment of each participant is at the discretion of the site PI
3. Patient is unable or unwilling to undergo any form(s) of SOC genetic testing
4. SOC testing is NOT requested for the participant

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Single Cohort; All participants will receive cWGS testing revealed to the site PI/clinician at Day 180. Participants will all receive standard of care testing throughout the study.	Other: clinical Whole Genome Sequencing; Participants will receive cWGS as well as standard of care testing. The clinician/site PI will be blinded to the cWGS results until Day 180.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Yield between cWGS and SOC testing	The number of participants who have a diagnosis in the SOC arm vs the cWGS arm as measured by the test outcome	Day 0 - Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Management between cWGS and SOC testing as measured by a management questionnaire collected on a case report form	The number of participants who have a change in management after receiving SOC results vs cWGS results as measured by a management questionnaire at baseline, Day 180 and Day 365	Day 0 - Day 365
Resource Utilization between cWGS and SOC testing	The number of participants who have utilized resources to include specialist referrals, tests/procedures ordered and procedures avoided in the SOC arm vs the cWGS arm as measured by data collection case report forms	Day 0 - Day 365
Quality of Life between cWGS and SOC testing	Comparison between Quality-of-Life scores as measured by the 12-Item Short Form Survey (SF12) from baseline compared to end of study	Day 0 - Day 365
Diagnostic Accuracy between cWGS and SOC testing when comparing the medical monitor test outcome and the site PI test outcome	Diagnostic accuracy- percent positive agreement between test outcome classified by the medical monitor and the site PI or designee	Day 0 - Day 180
Diagnostic Yield within Cohort when evaluating specific Neurologic disorders	Difference in diagnostic yield between cohorts of neurological disorders	Day 0 - Day 365

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Diagnosis between cWGS and SOC testing	Average time (in days) to diagnosis between SOC and cWGS testing (duration between when sample is approved and when result(s) is/are delivered)	Day 0 - Day 365
Clinical Survey by the clinician who ordered SOC testing	Clinician and genetic counselor satisfaction measured by an end-of-study questionnaire determining the overall satisfaction with the use of cWGS testing	Day 365
Participant Survey	Participant satisfaction measured by an end-of-study questionnaire determining the overall satisfaction with the use of cWGS testing Participant satisfaction measured by an end-of-study questionnaire determining the participant's overall satisfaction with the use of cWGS testing	Day 365

Collaborators and Investigators

• Sponsor: Illumina, Inc.
• Investigators: Study Chair: Ryan J Taft, Ph.D, Illumina, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2019
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital Abnormalities; Nervous System Diseases; Neurologic Manifestations; Nervous System Malformations
• Other Study ID Numbers: Neuro-R001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan in place to share data with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No