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Trial record 2 of 18 for:    "Hirschsprungs disease"

Hirschsprung Disease Genetic Study

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by Johns Hopkins University
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00478712
First received: May 24, 2007
Last updated: February 23, 2017
Last verified: February 2017
  Purpose
Hirschsprung disease is a genetic condition caused by lack of nerve cells in varying lengths of the intestines. This study will investigate the complex genetic basis of the disease, which involves multiple interacting genetic factors.

Condition Intervention
Hirschsprung Disease Other: Identification of genetic causes of Hirschsprung Disease

Study Type: Observational
Study Design: Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Genetic Analysis of Hirschsprung Disease

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Discovery and characterization of common genetic variation associated with Hirschsprung disease [ Time Frame: DNA is isolated up to 1 year after enrollment ]
    Genome-wide assays of common genetic variation will be assessed using single nucleotide polymorphism (SNP) arrays

  • Discovery and characterization of copy number variants associated with Hirschsprung disease [ Time Frame: DNA is isolated up to 1 year after enrollment ]
    Copy number variation will be detected using next generation sequencing data and high resolution microarrays that allow for detection of copy number variants across the genome

  • Discovery and characterization of rare genetic variation associated with Hirschsprung disease [ Time Frame: DNA is isolated up to 1 year after enrollment ]
    Exome sequencing will be used to detect rare variation across all genes in the genome


Secondary Outcome Measures:
  • Correlation of genetic variants with location of transition zone in Hirschsprung disease [ Time Frame: Baseline pathology data is obtained up to 1 year after enrollment ]
    Pathology records and surgical records will be used to determine transition zone

  • Correlation of genetic variants with risk for enterocolitis in Hirschsprung disease [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment ]
  • Characterization of Hirschsprung disease that co-occurs with a known chromosomal disorder [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment ]
  • Characterization of Hirschsprung disease that co-occurs with a known single gene syndrome [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment ]
  • Characterization of Hirschsprung disease that co-occurs with other congenital anomalies without a known diagnosis [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment ]
  • Correlation of genetic variants with need for repeat pull-through surgery in Hirschsprung disease [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment and follow up data is obtained up to 100 years after enrollment ]
    Assessment of complications that lead to eventual repeat pull-through surgery

  • Correlation of genetic variants with difficulty controlling stools after pull-through surgery [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment and follow up data is obtained up to 100 years after enrollment ]
  • Correlation of genetic variants with chronic constipation after pull-through surgery [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment and follow up data is obtained up to 100 years after enrollment ]

Biospecimen Retention:   Samples With DNA
Study volunteers are asked to provide blood or cheek swab/saliva samples. DNA is extracted from the samples for use in the study.

Estimated Enrollment: 3000
Study Start Date: January 2001
Estimated Study Completion Date: March 2025
Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Families with Hirschsprung Disease
Individuals with Hirschsprung disease and their affected and unaffected relatives.
Other: Identification of genetic causes of Hirschsprung Disease
Blood, saliva, or DNA samples are requested from all study participants. The blood or saliva samples are used to isolate DNA in all participants. Blood samples are also used to establish cell lines in some participants.

Detailed Description:

Hirschsprung disease (HSCR) is a birth defect resulting from the absence of nerve (ganglion) cells in the gastrointestinal tract. Hirschsprung disease has a population incidence of 1/5000 live births and most often occurs as an isolated condition. However, approximately 30% of HSCR cases are associated with other birth defects such as Down syndrome, deafness, hypopigmentation, and congenital central hypoventilation syndrome. Hirschsprung disease is a genetic condition with autosomal dominant, autosomal recessive, and multigenic patterns of inheritance described.

Dr. Aravinda Chakravarti's laboratory at Johns Hopkins University has been investigating the genetics of Hirschsprung disease (HSCR) for more than twenty five years. The goal of this research study is to identify genes harboring causative HSCR mutations and to better understand the complex inheritance of HSCR in families by whole genome mapping and sequencing studies. Specifically, the study aims to determine the frequency with which mutations in any human gene lead to familial and isolated forms of HSCR. Further, the study will collect clinical information and investigate possible genotype - phenotype correlations.

Molecular analysis using markers and sequencing, and statistical analysis of these data will be used to identify regions of human chromosomes where putative HSCR disease genes may be located. In addition, the DNA sequence of known and/or suspected HSCR genes will be assessed in individual patients and their family members, in search of causative HSCR susceptibility variants and variants that may affect presentation of the disease and treatment outcomes. Phenotypic information will include pathology, surgical, and other clinical outcomes related to Hirschsprung disease. This study will hopefully lead to a better understanding of the genetics of HSCR and, further down the road, improved diagnosis, treatment, and genetic counseling.

This study asks volunteers to:

  1. Complete a medical/family history questionnaire
  2. Provide access to some medical records
  3. Submit blood samples from the individual(s) affected with Hirschsprung disease and his/her parents (if available)
  Eligibility

Ages Eligible for Study:   up to 100 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The study population includes individuals with Hirschsprung disease and their family members.
Criteria

Inclusion Criteria:

- Individuals with Hirschsprung disease and their first degree relatives (any segment length of disease, with or without other congenital anomalies or health problems, single or multiple affected individuals in family)

Exclusion Criteria:

  • Unable or unwilling to provide sample for genetic studies
  • Individual, parent, or guardian unable to comprehend and provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478712

Contacts
Contact: Courtney Berrios, ScM 410-502-7541 hirschsprung@jhmi.edu
Contact: Aravinda Chakravarti, PhD 410-502-7525 hirschsprung@jhmi.edu

Locations
United States, Maryland
Institute of Genetic Medicine Recruiting
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Aravinda Chakravarti, PhD Johns Hopkins University
  More Information

Additional Information:
Publications:

Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00478712     History of Changes
Other Study ID Numbers: NA_00035221
Study First Received: May 24, 2007
Last Updated: February 23, 2017

Keywords provided by Johns Hopkins University:
Hirschsprung

Additional relevant MeSH terms:
Hirschsprung Disease
Digestive System Abnormalities
Digestive System Diseases
Megacolon
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Congenital Abnormalities

ClinicalTrials.gov processed this record on June 26, 2017