Identification of Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease

Status: Recruiting
Location: See location...
Study Type: Observational
SUMMARY

To identify demographic, clinical, genetic, immunologic and/or microbial (i.e., fecal stream characterization) risk factors that influence the likelihood of development of the HAEC phenotype in children who carry the diagnosis of HD. The newly formed HAEC Collaborative Research Group (HCRG) will utilize the 4 participating centers in the current consortia and recruit additional centers to enroll children diagnosed with Hirschsprung disease. 1a: To recruit 200 patients with Hirschsprung disease without HAEC. 1b: To recruit 200 patients with Hirschsprung disease and HAEC using standardized diagnostic criteria by collaborating with participating members of the HAEC Collaborative Research Group\[1\]. 1c: To collect clinical and demographic information from well-characterized HD patients both with and without HAEC. 1d: To collect samples blood for DNA for genome wide association study (GWAS) by high throughput SNP technology and mutational analysis of known HSCR genes. 1e: To collect serum samples at the time of recruitment in a subset cohort (n=50 HD only, n=50 HD + HAEC) for serological immune markers known for inflammatory bowel disease (IBD) including ANCA, ASCA, OMPC, I2, and CBir1 and any newly identified markers. 1f: To collect and store fresh fecal specimens for future evaluation by molecular methodologies to determine relative proportions of enteric microflora in a subset cohort (n=50 HD only, n=50 HD + HAEC) of children (\<18 years). 1g: To establish a Centralized Data Coordinating Center for data collection, data quality and detailed data analyses (CSMC) and tissue bank (CSMC) to facilitate specimen analysis for this study. The HAEC risk factor identification will be completed by multivariate logistic regression analysis. Genetic association will be studied for each SNP in the GWAS together with all other potential risk factors. Further analysis will be carried out to evaluate multiple SNPs/genes simultaneously.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1 day
Maximum Age: 17
Healthy Volunteers: f
View:

• 1\. Males and females of all ages with a confirmed diagnosis of HD based on standardized histological criteria. Only Males and females ages 0 to 17 with a confirmed diagnosis of HD based on standardized histological criteria will be enrolled at CSMC.

• 2\. Able to provide written informed assent if between the ages of 7 and 17. If age 6 and under, able to participate with parental permission.

• 3\. Have consented to have specimens tested for genetics, immune responses, stool microflora.

⁃ Case Ascertainment:

⁃ All patients with a confirmed diagnosis of HD are eligible for enrollment. A diagnosis of HD for this study will require:

• 1)Documented histopathology showing absence of ganglion cells and is consistent with the diagnosis of HD.

Locations
United States
California
Cedars-Sinai Medical Center 8723 Alden Drive, Suite 240
RECRUITING
Los Angeles
Contact Information
Primary
Philip K Frykman, MD, PhD, MBA
philip.frykman@cshs.org
310-423-6235
Backup
Denice M Dubuclet, DC
denice.dubuclet@cshs.org
310-423-6996
Time Frame
Start Date: 2010-02
Estimated Completion Date: 2025-12
Participants
Target number of participants: 400
Treatments
Subjects with HAEC
There is no intervention involvement. The clinical data and biologic specimens collected during the study will serve as an invaluable resource for a wide spectrum of clinical and translational ancillary studies directly related to the aims and goals of the study.
Subjects without HAEC
A subgroup of children who have Hirschsprung Disease may or may not develop enterocolitis; therefore we will be identifying the bio-markers in children with or without associated enterocolitis.
Sponsors
Collaborators: The University of Texas Health Science Center, Houston, UCSF Benioff Children's Hospital Oakland, University of Michigan, Karolinska University Hospital, Children's Hospital Los Angeles
Leads: Cedars-Sinai Medical Center

This content was sourced from clinicaltrials.gov