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Crohn's DiseaseNCT00783575

Genetic Markers as Predictors of Phenotypes in Pediatric Onset Crohn's Disease

An observational study of Crohn's Disease and Ulcerative Colitis, run by Medical College of Wisconsin at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to look for the NOD2 gene in children with Inflammatory Bowel Disease (IBD) and their parents. We hope to understand this NOD2 gene better by determining whether children that have IBD have the NOD2 gene. Read more about this study

Who is it for?
Ages Up to 18 years
How many people
0 participants
Where
1 siteUnited States
Study dates
Oct 2002to Jan 2015
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Study population: Children from Southeast Wisconsin diagnosed with Inflammatory Bowel Disease at Children's Hospital of Wisconsin and their biological parents.

Who may be able to join

  • Confirmed diagnosis of Inflammatory Bowel Disease (Crohn's Disease, ulcerative colitis or indeterminate colitis).

Who cannot join

  • Diagnosis during non-pediatric age.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

The purpose of this study is to look for the NOD2 gene in children with Inflammatory Bowel Disease (IBD) and their parents. We hope to understand this NOD2 gene better by determining whether children that have IBD have the NOD2 gene. In those with the NOD2 gene, we want to see if the type of gene abnormality predicts the nature of their disease and if the genetic information helps doctors decide what therapies and/or treatments to use for their patients. We also hope to explore the relationships between known serologic markers of IBD (ASCA, pANCA, ompC) and the clinical characteristics and course of children with IBD.

About 1500 children and as many of their parents as possible will take part in this study. Children who are newly diagnosed with IBD as well as children that are being seen in the Children's Health System are eligible to participate in this study. We are looking for children 18 years old or younger to participate. If possible, we would also like both parents of the child to participate.

Read the detailed description

Crohn's disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD) are chronic, life-long, destructive inflammatory conditions of the gastrointestinal tract. IBD onset can occur at any age but the highest incidence occurs in late childhood, adolescence and young adulthood. The incidence of IBD in children and adolescents has significantly increased over the last 40 years. The precise factors underlying IBD pathogenesis are not yet defined but may involve persistent bacterial infection, a defective mucosal barrier, or an imbalance in the regulation of the immune response. Epidemiologic studies from adult populations have identified a significant genetic contribution to the etiology of CD, but simple Mendelian models of IBD inheritance are not supported by segregation analysis. Taken together, these observations support a complex immunogenetic model of IBD whereby genetically susceptible individuals harbor an aberrant response to yet-unidentified environmental influences. Attempts to localize IBD susceptibility genes through genome-wide linkage studies have identified putative loci on chromosome 16. Recently 3 groups of investigators have shown that sequence variations within the NOD2 gene (MIM 605956) on chromosome 16q12 were strongly associated with susceptibility to CD. Attempts to link NOD2 mutations with disease phenotype have recently identified an association between ileal specific-disease and patients with NOD2/ CARD 15 mutations. This initial association between genotype and phenotype suggests that genetic factors influence disease location. At this time the frequency of NOD2 gene mutations in a population based sample, specifically in a cohort of newly diagnosed patients is not known. In addition, all attempts to correlate genotype with CD phenotype have been performed in adults, and no data has been generated in children. Identification of these mutations in children will be of particular interest, as the presentation of initial disease will manifest disease in its "purest" form, where the long duration of chronic inflammation typically seen in adult patients will not have exerted influence on disease phenotype (i.e. stricture formation secondary to longstanding, poorly controlled inflammation). Thus, genotype/phenotype correlation in children in a prospective fashion will function to characterize NOD2/ CARD15 mutations in a general population, and will also begin the evaluation of disease progression and prediction of disease severity and behaviour over time, with the starting point being the time of diagnosis. This will have obvious clinical and therapeutic implications, and will begin the process of linking disease genotype to optimal therapy. Therefore, our central hypothesis: Identification of NOD2/ CARD 15 mutations in newly diagnosed CD children will predict disease location, disease behaviour and will identify optimal approaches to therapy. This will be tested by the following three Specific Aims.

  1. Genotype a cohort of WI IBD children for 4 NOD2 / CARD 15 mutations.
  2. Statistical analysis of phenotype and genotype correlation in a cohort of WI pediatric IBD alliance children with or without a family history of IBD.

The Wisconsin pediatric IBD alliance was formed in January of 2000 to track all new diagnoses of IBD occurring in children younger than age 18. This clinical consortium has successfully recruited 100% of the pediatric GI specialists within Wisconsin to prospectively record all new IBD diagnoses, in order to obtain a population based incidence of CD and UC within the U.S. Between 1/1/00 and 12/31/01, we have identified 192 new cases of IBD within the state. Sixty-five percent of these children were from Southeast Wisconsin, and were diagnosed at Children's Hospital of Wisconsin. In addition to these newly diagnosed children, a cohort of 294 additional pediatric IBD children followed at the Children's Hospital of Wisconsin will serve as a reference population. The focus of this proposal will be to correlate genetic influence on the clinical disease course and behavior using a molecular classification of pediatric CD children in a population based pediatric cohort. This DDC grant will allow the PI and the co-investigator to generate sufficient preliminary data in the under-researched area of pediatric CD and to continue this investigation for support from national foundations (CCFA) and /or the NIH.

Keywords
Crohn's disease, Ulcerative colitis, Inflammatory bowel disease, NOD2,CARD 15 mutations
Medical subject headings
Crohn Disease, Colitis, Ulcerative, Inflammatory Bowel Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00783575
Study groupRoleWhat they receive
Inflammatory Bowel DiseaseCrohn's disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD) are chronic, life-long, destructive inflammatory conditions of the gastrointestinal tract.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Genotype a cohort of IBD children for 4 NOD2/CARD15 mutations.

    Measured: Study completion

Secondary outcomes (1)
  1. Statistical analysis of phenotype and genotype correlation in a cohort of pediatric Inflammatory Bowel Disease children with or without a family history of Inflammatory Bowel Disease

    Measured: Study completion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2008 (estimated)
  2. Study startOct 2002
  3. Primary completionJan 2015 (estimated)
  4. Study completionJan 2015 (estimated)

Why it stopped: PI has left institution

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Family based
Time perspective
Prospective
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00783575
Sponsor's protocol ID
CHW 02/142
Status last verified
Aug 2015
First submitted
29 Oct 2008
Last updated
24 Aug 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Sawczenko A, Sandhu BK, Logan RF, Jenkins H, Taylor CJ, Mian S, Lynn R. Prospective survey of childhood inflammatory bowel disease in the British Isles. Lancet. 2001 Apr 7;357(9262):1093-4. doi: 10.1016/s0140-6736(00)04309-9.

    PubMed 11297962
  • Orchard TR, Satsangi J, Van Heel D, Jewell DP. Genetics of inflammatory bowel disease: a reappraisal. Scand J Immunol. 2000 Jan;51(1):10-7. doi: 10.1046/j.1365-3083.2000.00656.x.

    PubMed 10632970
  • Ahmad T, Armuzzi A, Bunce M, Mulcahy-Hawes K, Marshall SE, Orchard TR, Crawshaw J, Large O, de Silva A, Cook JT, Barnardo M, Cullen S, Welsh KI, Jewell DP. The molecular classification of the clinical manifestations of Crohn's disease. Gastroenterology. 2002 Apr;122(4):854-66. doi: 10.1053/gast.2002.32413.

    PubMed 11910336
  • Podolsky DK. Inflammatory bowel disease (1). N Engl J Med. 1991 Sep 26;325(13):928-37. doi: 10.1056/NEJM199109263251306. No abstract available.

    PubMed 1881418
  • Podolsky DK. Inflammatory bowel disease (2). N Engl J Med. 1991 Oct 3;325(14):1008-16. doi: 10.1056/NEJM199110033251406. No abstract available.

    PubMed 1886623
  • Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, Naom I, Dupas JL, Van Gossum A, Orholm M, Bonaiti-Pellie C, Weissenbach J, Mathew CG, Lennard-Jones JE, Cortot A, Colombel JF, Thomas G. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature. 1996 Feb 29;379(6568):821-3. doi: 10.1038/379821a0.

    PubMed 8587604
  • Hampe, J. and S. Schrieber, A genome-wide search identies potential susceptibility loci for Crohn's disease. Am J Hum Genet, 1999. 64: p. 808-16.

  • Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):599-603. doi: 10.1038/35079107.

    PubMed 11385576
  • Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):603-6. doi: 10.1038/35079114.

    PubMed 11385577
  • Calkins, B.M., Inflammatory Bowel Diseases, in Digestive Diseases in the United States: Epidemiology and Impact, J.E. Everhart, Editor. 1994, U.S. Government Printing Office: Washington D.C. p. 509-550.

  • Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol. 1996 Mar;91(3):423-33. No abstract available.

    PubMed 8633486
  • D'Haens GR, Gasparaitis AE, Hanauer SB. Duration of recurrent ileitis after ileocolonic resection correlates with presurgical extent of Crohn's disease. Gut. 1995 May;36(5):715-7. doi: 10.1136/gut.36.5.715.

    PubMed 7797122
  • Loftus EV Jr, Schoenfeld P, Sandborn WJ. The epidemiology and natural history of Crohn's disease in population-based patient cohorts from North America: a systematic review. Aliment Pharmacol Ther. 2002 Jan;16(1):51-60. doi: 10.1046/j.1365-2036.2002.01140.x.

    PubMed 11856078
  • Barton JR, Gillon S, Ferguson A. Incidence of inflammatory bowel disease in Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-fold rise in Crohn's disease. Gut. 1989 May;30(5):618-22. doi: 10.1136/gut.30.5.618.

    PubMed 2786488
  • Cosgrove M, Al-Atia RF, Jenkins HR. The epidemiology of paediatric inflammatory bowel disease. Arch Dis Child. 1996 May;74(5):460-1. doi: 10.1136/adc.74.5.460.

    PubMed 8669968

Questions about this trial

What is this clinical trial studying?

An observational study of Crohn's Disease and Ulcerative Colitis, run by Medical College of Wisconsin at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 24 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Genotype a cohort of IBD children for 4 NOD2/CARD15 mutations. (time frame: Study completion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00783575, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2015.

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