Telomere Repair Gene Mutation in Inflammatory Bowel Disease

Telomere Repair Gene Mutations in Inflammatory Bowel Disease

This study will evaluate and compare the genes of the telomere repair complex in healthy control subjects, patients with blood diseases, and patients with inflammatory bowel disease to identify what, if any, changes are associated specifically with inflammatory bowel disease.

Patients between 2 and 80 years of age with ulcerative colitis or regional enteritis may be eligible for this study. Participants are recruited from the practice of Dr. Stuart Danovitch, Washington, D.C.

Researchers have established that minor differences in a specific set of genes called the telomere repair complex are related to immune-mediated diseases of the bone marrow. NIH researchers are now interested in whether inflammatory bowel disease and other autoimmune diseases show a similar pattern of genetic differences.

Participants provide a cell sample for evaluation of the telomere repair complex. The sample is collected via buccal swab, a gentle scraping of the inside of the cheek, and stored for use in research.

Study Overview

Status

Completed

Detailed Description

We have identified inherited mutations in genes of the telomere repair complex in patients with acquired aplastic anemia. These mutations diminish the ability of cells to repair the ends of chromosomes, called telomeres, which normally shorten with each cell division. Mutations in TERC, the gene which encodes for the RNA template of the complex; in TERT, the gene for the enzyme in the complex, and also in the Schwachman-Bodian-Diamond syndrome gene (SBDS), which we believe to be associated with telomere repair, lead to reduced telomerase activity, diminished numbers of hematopoietic cells in the bone marrow, and presumably also a deficiency in the ability of cells to respond to immunological attack and destruction of the hematopoietic system.

This laboratory research protocol will allow us to evaluate whether similar gene mutations might underlie other autoimmune diseases, here specifically, inflammatory bowel disease, which share broad pathophysiologic features with immune-mediated aplastic anemia. We will directly assess by DNA sequencing suspect genes (TERC, TERT, SBDS, DNA helicases and others) in buccal mucosal samples obtained from patients with inflammatory bowel disease (IBD). Analyses from large numbers of controls have defined polymorphisms for these genes. IBD samples will allow us to determine whether mutations in these genes are more prevalent in this patient population and to test the hypotheses that telomere repair defects underlie human autoimmunity, or that these genes are specifically involved in hematology as risks factors for bone marrow failure.

Study Type

Observational

Enrollment (Actual)

95

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 80 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects with Inflammatory Bowell Disease

Description

  • INCLUSION CRITERIA:

Diagnosis of ulcerative colitis or regional enteritis

For adults:

Ability to comprehend the investigational nature of the study and provide informed consent. Or

For minors: Written informed consent from one parent or guardian and informed assent. The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.

Age greater than 2 but less or equal to 80 years old

EXCLUSION CRITERIA:

All subjects not fulfilling the inclusion criteria will be considered ineligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
IBD subjects
Subjects with Inflammatory Bowell Disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To identify if telomere repair complex gene mutations are abnormally prevalent among patients with IBO.
Time Frame: Ongoing
To identify if telomere repair complex gene mutations are abnormally prevalent among patients with IBO.
Ongoing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To correlate telomere repair gene mutations in subjects with immune mediated disease stratified based on diagnosis as they relate to clinical course and response to therapy.
Time Frame: Ongoing
We aim to correlate telomere repair gene mutations in subjects with immune mediated disease stratified based on diagnosis with clinical course and response to therapy.
Ongoing
To compare the telomere repair gene mutations of normal individuals (from large populations studies in the public domain) as well as to those of patients with known bone marrow failure
Time Frame: Ongoing
We aim to compare the telomere repair gene mutations of normal individuals with those of patients with known bone marrow failure
Ongoing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2006

Primary Completion (Actual)

May 15, 2006

Study Completion (Actual)

May 21, 2020

Study Registration Dates

First Submitted

July 18, 2006

First Submitted That Met QC Criteria

July 18, 2006

First Posted (Estimate)

July 19, 2006

Study Record Updates

Last Update Posted (Actual)

May 22, 2020

Last Update Submitted That Met QC Criteria

May 21, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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