Infectious Agents in Pediatric Crohn's
|First Received Date ICMJE||October 11, 2005|
|Last Updated Date||March 17, 2010|
|Start Date ICMJE||August 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00237055 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Infectious Agents in Pediatric Crohn's|
|Official Title ICMJE||Infectious Agents in Pediatric Crohn's Disease|
Six sites of the Pediatric Inflammatory Bowel Disease Consortium (plus 2 additional sites) will participate in this study. The participating sites will be that of the Principal Investigator (PI), Emory University School of Medicine, Atlanta, GA (Benjamin D. Gold, MD); Texas Children's Hospital / Baylor College of Medicine (George Ferry, MD and Tony Olive, MD); Children's Hospital of Philadelphia, Philadelphia, PA (Bob Baldassano, MD); University of Chicago Children's Hospital, Chicago, IL (Barbara Kirschner, MD); University of California, San Francisco (Mel Heyman, MD); Mass General Hospital / Harvard University (Harland Winter, MD); V.A. Stanford University School of Medicine, Stanford, CA (David Relman, MD); Children's Center For Digestive Healthcare, Atlanta, GA (Stanley Cohen, MD); and Centers for Disease Control and Prevention, Atlanta, GA (Drs. Jeannette Guarner, Siobhan O'Connor and Thomas Shinnick)
The duration of study is 2 yrs.
The study design involves children ages 6 months through 17 11/12 years of age who are undergoing a clinically-indicated colonoscopy. Subjects will be grouped into cases and controls.
Inflammatory bowel disease (IBD), which includes CD and ulcerative colitis (UC), is estimated to affect approximately 1 - 2 million Americans. Recent studies strongly suggest that these disorders are increasing in prevalence in developed and developing countries, and in first generation immigrants to industrialized nations. Changing epidemiology of IBD implies that, in addition to a genetic susceptibility for disease, an environmental trigger or exposure likely impacts disease expression. However, the specific pathobiology and etiology of IBD remain unclear. Knowledge of the host genetic basis of IBD has advanced, including characterization of a novel susceptibility gene in adult and adolescent CD (NOD2/CARD-15) located on the pericentromeric region of chromosome 16. Recent studies not only implicate NOD2/CARD-15 in susceptibility to CD, but also suggest a link between the innate immune response to bacterial components and development of disease. Thus, well-designed investigations of infectious etiologies of CD, with sufficient power to detect differences in infection between IBD and non-IBD patients, are critically needed. Yet, deficiencies in the methods and tools for such studies still exist.
Both infectious and noninfectious mechanisms of pathogenesis remain plausible but unconfirmed. To date, scientific evidence cannot conclude whether one or more infectious pathogens triggers or determines the development and outcomes of CD or UC. Persistent exposure to "normal resident flora" in an abnormally permeable gut might also conceivably determine disease. Thus carefully designed investigations that apply systematically evaluated, reliable and reproducible detection assays are needed to confirm or disprove infectious hypotheses of causation. The first step is a pilot study that validates study design and complementary assays (morphology-, molecular- and culture-based) and uniformly applies these to target patient and control tissues (i.e., pediatric endoscopic biopsies). It must focus on newly diagnosed CD (surrogate for "incident" CD) in a well-characterized group of patients and appropriate, well-selected controls who meet uniform case and control definitions. It must develop reproducible methods to ensure that results from different studies can be compared and appropriate clinical interpretations made in order to translate research results into treatment and prevention strategies that decrease the burden of CD. At this time, deficiencies in both methodology and laboratory technology impede successful conduct and interpretation of the needed studies on causality.
Based on age of onset, newly diagnosed children with IBD, may be closer to triggering immunopathogenic events that initiate the inflammatory response than adults. They may also represent a unique population for the study of environmental factors (e.g., infection), i.e., younger age usually brings shorter and less complicated exposure histories to confound analyses. It is reasonable to postulate that a single agent or polymicrobial insults, in the genetically susceptible host, may determine the development or course of CD and it may be easier to identify some infectious determinants in childhood CD. We hypothesize that adequate collection of intestinal tissue biopsies from uniformly defined pediatric CD cases and controls and validation of sensitive and specific laboratory tools to detect potential infectious triggers of CD in these particular specimen types are needed to test causality for infection in CD. The Pedi IBDC, 6 large, geographically diverse U.S. centers represents an excellent platform to investigate potential infectious factors in CD, annually evaluating and recording clinical and epidemiologic data on ~288 newly diagnosed pediatric CD cases in a comprehensive data repository. The Pedi IBDC has a system to assess the safety and efficacy of its research. The Consortium also provides a pool of cases and controls in which to implement standardized specimen collection techniques under a well-conceived algorithm. The R03 assembled research team draws on a wide range of expertise and institutional resources in epidemiology, infectious disease pathology, molecular microbiology, mycobacteriology and virology, and the conduct of clinical trials. The multi-disciplinary expertise of this proposal can test and validate in small endoscopic biopsies the histopathology and molecular microbial detection assays previously validated in alternative paraffin-embedded or frozen tissues.
The R03 funding mechanism will facilitate tissue collection and banking techniques and evaluations of a panel of assays to detect select infectious agents ranging from those thought not to cause CD to those speculated as etiologic, from non-pathogenic commensals to known and undetermined pathogens. Therefore, our specific study aims are to:
Additionally, molecular characterization of microbiota in the feces from cases and controls will be compared to microbial detection in their respective tissue biopsies. Successful completion of these goals will provide a platform for imminent comprehensive investigations that characterize clinically relevant microbial risk factors for CD in the child and quite possibly the adult patient.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Groups/Cohorts||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Enrollment ICMJE||500|
|Estimated Completion Date||September 2006|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Each subject must satisfy all of the following inclusion criteria to be considered eligible for entry into this study:
Patients with any of the following characteristics will NOT be eligible for entry into the study:
|Ages||6 Months to 18 Years (Child, Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00237055|
|Other Study ID Numbers ICMJE||R03 DK64544 (completed), NIDDK R03 DK64544|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Verification Date||March 2010|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP