Gene Mutations and Rescue in Human Congenital Diaphragmatic Hernia

• Conditions: Congenital Diaphragmatic Hernia

• Registration Number: NCT01098929
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

Congenital diaphragmatic hernia (CDH) occurs when the diaphragm, the muscle that separates the chest cavity from the abdominal cavity, does not form properly. When an opening is present in the diaphragm, organs that are normally found in the abdomen can move up into the chest cavity. The primary objective of this study is to generate information about the hereditary basis of congenital diaphragmatic hernia and abnormal lung development. Our long-term goal is to identify ways to treat babies in utero with effective but safe drugs to speed up lung development before birth.

Detailed Description

This study uses a combination of clinical, molecular biological, and developmental strategies to better understand the genetic basis of congenital diaphragmatic hernia. Ongoing projects at Massachusetts General Hospital include identification of novel genes affecting diaphragm and lung development in a) mouse models using laser capture, microdissection, expression arrays, and statistical and bioinformatics analysis and b) human kindreds with multiple affected family members using linkage analysis and exome sequencing.

Research projects based at Children's Hospital Boston include a) continued recruitment of a population of patients with congenital diaphragmatic hernia who are carefully phenotyped for entry into an extensive database, b) collection of biological samples belonging to the phenotyped cohort of patients, c) next-generation sequencing on candidate genes and d) molecular cytogenetic studies such as comparative genomic hybridization and subtelomeric fluorescence in situ hybridization.

Over 500 patients with congenital diaphragmatic hernia and their families have been recruited to date and efforts are ongoing to double this number. The investigators hope that the information gained through identifying the genes that contribute to congenital diaphragmatic hernia will provide the foundation for future efforts to develop effective interventions for the treatment of this disease.

Study Timeline

• Study Start: 2002-07
• Study First Submitted: 2010-03-31
• Study First Submitted QC: 2010-04-02
• Study First Posted: 2010-04-05
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-16
• Last Update Posted: 2015-12-17
• Primary Completion: 2017-07
• Study Completion: 2017-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

All individuals affected with a congenital diaphragmatic hernia (CDH), or with a family history of CDH

Exclusion Criteria

Individuals with no personal or family history of a CDH

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
identify genes associated with CDH	5 years

Trial Locations

Locations (1)

Children's Hospital Boston; 🇺🇸 Boston, Massachusetts, United States