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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Neurologic Deficits, Neurologic Disorder, Neurologic Abnormalities

Intervention / Treatment
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* Other: clinical Whole Genome Sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years at the time of consent Participant is referred to a Neurogenetics Program due to suspected genetic etiology of a neurological syndrome No history of prior genetic testing for the suspected condition in the participant or any family member with a similar phenotype Must be able to have one - 4 to 6 ml tube of whole blood drawn for testing 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: Any known non-genetic cause(s) of disease, disorder, or phenotypic defect Eligibility for enrollment of each participant is at the discretion of the site PI Patient is unable or unwilling to undergo any form(s) of SOC genetic testing SOC testing is NOT requested for the participant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Single cohort who receives standard of care testing prior to the results from cWGS.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single Cohort<br>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<br>* 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.<br>|

What is the study measuring?
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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 |