North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2 — NCGENES2  

Autism Spectrum Disorder Clinical Trial

Official title: North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2

Status Active, not recruiting

Clinical Trial Summary

The "North Carolina Clinical Genomic Evaluation by Next-gen Exome Sequencing, 2 (NCGENES 2)" study is part of a larger consortium project investigating the clinical utility, or net benefit of an intervention on patient and family well-being as well as diagnostic efficacy, management planning, and medical outcomes. A clinical trial will be implemented to compare (1) first-line exome sequencing to usual care and (2) participant pre-visit preparation to no pre-visit preparation. The study will use a randomized controlled design, with 2x2 factorial design, coupled with patient-reported outcomes and comprehensive clinical data collection addressing key outcomes, to determine the net impact of diagnostic results and secondary findings.

Clinical Trial Description

The NCGENES 2 study is part of the "Clinical Sequencing Evidence-Generating Research (CSER2)"

• Clinical Sites with Enhanced Diversity (U01), and brings together interdisciplinary experts from across North Carolina to address questions critical to the translation of genomic medicine to the care of patients with suspected genetic disorders.

In this renewal of the initial NCGENES study, NCGENES 2 will carry out a clinical trial of exome sequencing as a diagnostic test to answer the next set of questions vital to making genome-scale sequencing a routine clinical tool. The study population will be drawn from a state-wide network of Clinical Genetics and Pediatric Neurology clinics -- clinical domains in which patients are enriched for phenotypes caused by heterogeneous genetic conditions. Exome sequencing and genome sequencing (ES/GS) are efficient means of establishing a molecular diagnosis in these populations, with yields of positive or possible diagnostic results in at least 30% of patients examined based on findings from NCGENES and other work. Evidence will be generated regarding the clinical utility of ES/GS using a prospective randomized controlled trial that compares usual care plus exome sequencing to usual care. Patient-reported data, electronic health records data, and administrative claims data will be used to evaluate defined health outcomes, in collaboration with experts in health economics and health services research, to address pressing questions about the utility of exome sequencing. Furthermore, an examination of communication between patients and physicians, and between physicians and laboratories, and how these critical interactions affect the utility of genomic sequencing will be conducted. A second, nested randomized trial (crossed with exome sequencing in a full-factorial design) will be incorporated to test the hypothesis that a theory-based, multi-component pre-clinic preparation intervention for patients will improve patient-centered outcomes. An "embedded Ethical, Legal, and Social Implications (ELSI)" component will provide feedback to providers regarding communication discrepancies to iteratively improve care. Finally, the challenges of integrating clinical data and genomic information across a state-wide network of sites and examining different models of interaction between genomic clinicians and molecular diagnostic laboratorians will be explored. ;

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Brain Malformation
• Chromosome Aberrations
• Chromosome Abnormality
• Chromosome Disorders
• Congenital Abnormalities
• Congenital Abnormality
• Development Delay
• Dysmorphic Features
• Epilepsy; Seizure
• Genetic Disease
• Genetic Diseases, Inborn
• Hearing Loss
• Hypotonia
• Inborn Errors of Metabolism
• Intellectual Disability
• Macrocephaly
• Metabolism, Inborn Errors
• Microcephaly
• Movement Disorders
• Neuromuscular Diseases
• Seizures
• Skeletal Dysplasia

• NCT number: NCT03548779
• Study type: Interventional
• Source: University of North Carolina, Chapel Hill
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 28, 2018
• Completion date: September 8, 2024