Whole Genome Sequencing Versus Whole Exome Sequencing for Congenital Diarrhea and Enteropahty

Study Overview
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Brief Summary
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This study will seek to determine if whole genome sequencing (WGS) improves diagnostic rates, and outcomes for congenital diarrhea and enteropathy (CODE) patients. The investigator will enroll 180 patients in a randomized controlled study to either WGS or whole exome sequencing (WES). This study is designed to evaluate whether CODE patients would benefit from WGS guided precision medicine.

Official Title
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A Randomized, Controlled Trial of the Effectiveness of Whole Genome Sequencing Versus Whole Exome Sequencing for Screening Patients With Congenital Diarrhea and Enteropathy (CODESeq)

Conditions
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Enteropathy, Diarrhea, Infantile

Intervention / Treatment
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* Genetic: Whole genome sequencing
* Genetic: Whole exome sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with chronic diarrhea lasting greater than 2 months Patients with consent from parents or legal guardians Biological relative of a patient enrolled in this study. Exclusion Criteria: Chronic diarrhea caused by specific infections, i.e. CMV, Clostridioides difficile Chronic diarrhea with necrotizing enterocolitis, short bowel syndrome Functional diarrhea Patients with previously confirmed monogenic diarrhea Patients with poor compliance

Ages Eligible for Study
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Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whole genome sequencing<br> | Genetic: Whole genome sequencing<br>* Genomic sequencing and molecular diagnostic results<br>|
| Active Comparator: Whole exome sequencing<br> | Genetic: Whole exome sequencing<br>* Genomic sequencing and molecular diagnostic results<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic rates between WGS and WES | Diagnostic rate of genome and exome based on rate of clinically confirmed diagnoses. | Within approximately 60 days of enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients receiving precision medicine guided by sequencing results | Rate of application of precision medicine suggested by the results of WGS or WES. | Within approximately 60 days of enrollment | 
| Mortality of patients | Mortality of patients after WGS and WES | Within approximately 1 year of enrollment | 
| Rate of parental satisfaction with sequencing | Parental satisfaction with decision to pursue sequencing based on questionnaire survey | Within one week of patient enrollment | 
| Number of parents who are available for trio sequencing | Number of subjects in which both parents are available for trio sequencing | Within one week of patient enrollment |