Gene Expression in Inflammatory Bowel Disease

NCT ID: NCT01171872

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 1100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 1999-11-30
• Study Completion Date: 2032-12-31

Brief Summary

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a idiopathic, chronic and frequently disabling inflammatory disorder of the intestines characterized by a dysregulated mucosal immune response that affect more than a million Americans. This protocol is aimed at obtaining tissue samples to test for expression of genes associated with IBD and to better understand the pathogenesis of IBD with the study of genetics, proteomics, physiologic processes and microbiomes (microbiology).

Detailed Description

Progress has been made in recent years in understanding the pathological mechanisms of IBD, particularly in the search of IBD susceptibility genes. However, due to the extreme complexity of the diseases, there is still a long way ahead in elucidating detailed molecular mechanisms of IBD pathogenesis and identifying more effective therapeutic targets. Therefore, it is the goal of this research study to discover genetic, microbial, gene expression and serological factors involved in the pathogenesis of IBD which may pave the way for the identification of more effective therapeutic targets.

The specific aims for these objectives are as follows:

AIM 1: Identify proteins that are changed in expression and post-translational modification in the intestinal mucosa of patients with active UC or CD compared to i) uninvolved intestinal mucosa from the same patients, ii) normal intestinal mucosa in control subjects, and iii) infectious/Inflammatory colitis (C. difficile colitis).

AIM 2: Identify changes in the expression of intestinal membrane transporters for Na absorption and Cl secretion, including NHE3, in the intestinal mucosa of patients with active UC or CD compared to i) uninvolved intestinal mucosa from the same patients, ii) normal intestinal mucosa in control subjects, and and iii) infectious/Inflammatory colitis (C. difficile colitis). The targeted screening will also include several intestinal epithelial brush border-associated PDZ-containing proteins that have been recently shown to regulate trafficking and activity of membrane transporters.

AIM 3: Enteroid Sub-study - To compare the physiologic regulation of Na absorption, Cl secretion, protein secretion and other intestinal physiologic processes in IBD cases, other infectious colitis cases and healthy controls as these processes are often altered with disease activities. The processes will be studied through the development of self-propagating culture models called organoids or enteroids. The culture models are developed from biopsy specimens taken from the upper small intestine, including duodenum and jejunum , lower small intestine (ileum) and proximal and distal colon and used to grow organoids/enteroids. These are mini-intestines that have the entire crypt villus axes which grow in culture and can be kept alive indefinitely in culture.

AIM 4: Mechanism of Intestinal Inflammation Sub-study - To understand the mechanisms involved in the recurrence of inflammation following ileal resection surgery for Crohn's disease (CD). Reasons for recurrence are currently unknown but are believed to be caused by an interaction of genetic, immune and microbial features. Information gained from this study will be used to build a predictive model to identify those patients at greater risk of rapid recurrence, and will aid physicians in tailoring follow-up treatments.

AIM 5: UC Demarcation Sub-study - To gain further understanding of the mechanisms involved in the susceptibility to and flare of inflammation in UC patients. Blood, stool, urine, saliva, lavage and tissue samples from UC patients will be used to help study the genetic, microbial, metabolic, and immune factors involved in the remission and flare of disease. Information gained from this study will also be used to build a predictive model of which patients are at greater risk of disease flare, and which are less likely to do so, allowing physicians to tailor follow-up treatments accordingly.

Conditions

Inflammatory Bowel Disease

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Unaffected

Individuals who do not have IBD

No interventions assigned to this group

Affected

Individuals who have IBD

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• All persons, regardless of IBD affection status, greater than 7 years of age undergoing upper or lower endoscopy or bowel resection

Exclusion Criteria

• Persons with bleeding tendencies
• Persons on anti-coagulation therapy or who will be place on anti-coagulation therapy following the planned endoscopy procedures

• Minimum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Florin Selaru, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

U01DK062431

Identifier Type: NIH

Identifier Source: secondary_id

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R24DK099803

Identifier Type: NIH

Identifier Source: secondary_id

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P01AI125181

Identifier Type: NIH

Identifier Source: secondary_id

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NA_00038329

Identifier Type: -

Identifier Source: org_study_id