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Johns Hopkins Crohn's Disease and Ulcerative Colitis Study

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2011 by Johns Hopkins University.
Recruitment status was:  Recruiting
ClinicalTrials.gov Identifier:
First Posted: July 26, 2010
Last Update Posted: July 8, 2011
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
Johns Hopkins University
This research is being done to find out why Inflammatory Bowel Disease (IBD) (i.e., Crohn's disease and ulcerative colitis) occurs in individuals and in families. Recently the investigators and other researchers have found a gene (DNA) that when changed, gives people a higher risk for developing IBD or other inflammatory diseases like IBD. By doing this research, scientists and doctors will study the cells in the blood to see how the gene-change affects the way the blood cells' immune system works.

Inflammatory Bowel Disease

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Johns Hopkins Crohn's Disease and Ulcerative Colitis Study

Resource links provided by NLM:

Further study details as provided by Johns Hopkins University:

Biospecimen Retention:   Samples With DNA
whole blood, serum

Estimated Enrollment: 2500
Study Start Date: July 1996
Individuals who do not have IBD
Individuals with IBD

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Detailed Description:

The inflammatory bowel diseases (IBD)—Crohn's disease (CD) and ulcerative colitis (UC) have an estimated combined prevalence of 0.2% to 0.3% in the United States, and are two to eight times more prevalent in Jewish Americans of Central or Eastern European descent (Ashkenazi Jews) as compared to non-Jewish Americans. CD may involve any part of the gastrointestinal tract, but most often the colon and terminal ileum. Bowel inflammation is discontinuous, transmural, and may contain granulomas. CD is also associated with bowel stenoses and intestinal and perianal fistulas. UC, by contrast, involves continuous, non-granulomatous inflammation of the colon and rectum, limited to the mucosal layers. Fistulas are not observed. Colonic disease that cannot be clearly identified as CD or UC is designated "indeterminate colitis".

There is strong evidence from twin studies and familial aggregation that CD and UC are in large part genetic, and follow a complex, non-Mendelian mode of inheritance. First-degree relatives of IBD patients have an 8 to 10 fold increased risk of developing IBD. Therefore, it was hypothesized that IBD is in part the result of mutations and disease polymorphisms in specific susceptibility genes. Furthermore, the complications, site of disease, onset and severity show increased familial concordance. Therefore, these and perhaps other factors in variability of disease expression and course appear to be in part under genetic control. The hypothesis is that familial disease aggregation is the result of IBD susceptibility genes disease risk polymorphisms and mutations. Loci containing these disease genes can be identified by linkage mapping and the disease gene polymorphisms can be determined by showing linkage disequilibrium (LD) with the disease variant greater in affected IBD cases as compared to within family (parental) or unrelated, matched controls. Power analyses show that to have 80% power to only identify IBD susceptibility loci with a relative sibling risk of 1.5 and an error of p = 0.01 and heterogeneity of 0.3 would require a genome screen on approximately 200 affected relative pair pedigrees. It would require several times this number of pedigrees to have power to establish these loci at genome wide levels of significance (Brant and Shugart, Inflamm Bowel Dis, 2004). To have power to establish (at p = 10-7) disease specific risk polymorphisms by LD association analyses—for genotypic relative risks of 2.0 with complex models of inheritance would require 350 to 700 cases and 350 to 700 controls or a similar number of parental/affected offspring "trio" pedigrees (i.e. up to 1400 parents with 700 affected offspring) (Knapp, AJHG, 1999). To establish lower relative risk polymorphisms would require about three times these numbers.

The current protocol was initiated in 1996 to initially collect multiplex pedigrees for linkage studies. The investigators performed the first IBD genome screen in North America in 1998 with DNAs from pedigrees collected from the study combined with those from the Univ. of Chicago and identified multiple loci, and confirmed the IBD1 locus on chromosome 16. In 2003, the investigators published a second genome wide screens that also included a large series

of patients recruited at Johns Hopkins under this protocol identifying and comfirming additional loci. The investigators (and others) have identified 8 confirmed IBD loci (IBD1-8), and there are several additional loci with strong evidence in one or more screens (Brant and Shugart, Inflamm Bowel Dis., 2004). The investigators have recently received funding for a new genome screen performed at the NIH funded Center for Inherited Disease Research (CIDR) genotyping facility, and samples are being submitted at this time. From these multiple loci, three proven disease genes for IBD have been established; the most provocative is the NOD2/CARD15 gene for the IBD1 locus. This gene is an intracellular sensor of bacterial cell wall components and a critical player in the innate immune system known to be important in IBD pathogenesis (Hugot et al and Ogura et al; Nature, 2001). The investigators participated in this discovery (Ogura et al., Nature, 2001).

There are three independent mutations in the NOD2 gene (G908R, R702W, and Cins1007fs) that are consistently increased in white CD patients as compared to healthy controls. These mutations interfere with the gene's ability to sense muramyl dipeptide, the critical bacterial cell wall residue. The investigators added to the protocol in 2001 permission to study isolated cells and biomarkers from larger blood withdrawals from study subjects and the investigators have found evidence for NOD2 gene expression variants. The two other established genetic factors are haplotype associations in the HLA region (IBD3) and the chromosome 5q cytokine cluster (IBD5, leading candidate are functional mutations in the OCTN1/2 genes). The investigators have also identified NFKB1 and MDR1 IBD predisposing polymorphisms.

Despite the exciting discoveries of multiple genes associated with IBD, altogether, these genes account of only a fraction of familial risk. Therefore, the investigators will continue to enroll participants to meet the present goal for recruitment of 2,500 samples composed of IBD pedigrees for linkage and familial LD studies, and singleton cases and controls for case-control LD association studies. The investigators will also work to discover if there is association of the genes with biomarkers from serum (the investigators have examined anti-Saccharomyces cerevisiae antibody and NOD2), and cells from blood and immortalized blood from IBD patients as compared to controls. In addition, the investigators will test biomarkers to evaluate their potential as predictors of disease course and therapeutic outcome.


Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   4 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
IBD patient's are primarily recruited at the Johns Hopkins inpatient and outpatient units. However, individuals contact us by phone, mail or email after hearing about our study

Inclusion Criteria:


  • Patients with IBD and their family members who have or do not have IBD.
  • People that do not have IBD nor have a family member with IBD needed for comparison purposes.
  • The age inclusion criterion for the Multiple Blood Draw (MBD) is 18 years of age or older.


  • Children greater than age 4 with IBD and their family members who have or do not have IBD.
  • People that do not have IBD nor have a family member with IBD needed for comparison purposes.

Exclusion Criteria:

  • The only exclusions are age parameters and health reasons that would preclude their enrollment; such as, for anemic patients. Blood-draws on anemic patients may, in certain medical cases, pose a health risk to them; therefore, we request that if they are anemic that they present a letter from their personal physician giving explicit permission for them to join if at the time it is clinically advisable.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01169207

Contact: Patricia Ushry 1(888) 279-4194 ibd@jhu.edu
Contact: Denise Spears, B.A. (410) 502-5846 dspears1@jhmi.edu

United States, Maryland
Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: Patricia Ushry    888-279-4194    ibd@jhu.edu   
Contact: Denise Spears    (410) 502-5846    dspears@jhu.edu   
Principal Investigator: Steven R Brant, M.D.         
Sponsors and Collaborators
Johns Hopkins University
Principal Investigator: Steven R Brant, M.D. Johns Hopkins University
  More Information

Responsible Party: Steven R. Brant, M.D., Johns Hopkins University-School of Medicine
ClinicalTrials.gov Identifier: NCT01169207     History of Changes
Other Study ID Numbers: 96-01-31-06
First Submitted: July 23, 2010
First Posted: July 26, 2010
Last Update Posted: July 8, 2011
Last Verified: July 2011

Keywords provided by Johns Hopkins University:
Inflammatory Bowel Disease
Crohn's Disease
Ulcerative Colitis
Indeterminate Colitis

Additional relevant MeSH terms:
Crohn Disease
Colitis, Ulcerative
Intestinal Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Pathologic Processes