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Risk Factors for Gastric Disease in Pediatric Helicobacter Pylori (H. Pylori)

This study has been completed.
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00212225
First received: September 20, 2005
Last updated: January 12, 2010
Last verified: January 2010
  Purpose

Helicobacter pylori (Hp) is a major cause of chronic-active gastritis and primary duodenal ulcers, and is strongly linked to gastric cancer. Most Hp infections worldwide are acquired in childhood. Why some individuals develop symptomatic disease is unclear and, until recently, no studies critically evaluated the role of pediatric Hp strains and/or host factors in disease outcomes. Over the past 5 years of National Institutes of Health (NIH) funding, 486 children from Atlanta, Cleveland, and Miami were enrolled; 184 (38%) were Hp-infected. Race (African American) and younger age, in conjunction with Hp strains expressing cagA and vacAs1B, were shown to be risk factors for both esophageal and gastric disease, suggesting a different disease paradigm from Hp-infected adults. Using the updated Sydney system, the investigators demonstrated a histopathologic spectrum in children, which included novel observations of atrophic gastritis with intestinal metaplasia.

Overall hypothesis for competitive renewal: disease manifestations in Hp-infected children are influenced by specific host factors (i.e., race, immune phenotype), environmental exposures, and specific virulence factors of infecting Hp strains.

Specific aims:

  1. Using well defined cases and controls, further characterize specific host factors and environmental exposures contributing to symptomatic childhood infection emphasizing targeted enrollment in specific age, gender and demographic strata to facilitate detection of significant differences not attained previously and follow-up of 2 established specific cohorts to ascertain immune response natural history.
  2. Utilize gene-array technology for the whole Hp genome assessment and bacterial gene expression of specific virulence determinants associated with pediatric Hp strains.
  3. Further characterize the host immunologic and mucosal response in Hp-infected children.

Hp-infected symptomatic endoscopy cases at the investigators' established 3 clinical centers of high, moderate and low Hp prevalence will be compared with age-matched Hp-infected asymptomatic and uninfected symptomatic controls. Two geographically and demographically distinct centers have been added to provide additional geographic and subject representativeness to the patient cohort. The updated Sydney system will be employed to assess gastric histopathology severity and phenotype in newly enrolled cases in specific age, gender and demographic strata and follow-up of the two "novel" cohorts established in the past 5 years: a) atrophic gastritis; and b) esophageal and gastric disease groups enabling a comprehensive, multivariate evaluation of the natural history of Hp-infected children in two distinct disease paradigms.

Using molecular methods (multiplex [MP]-PCR, RT-PCR) and a micro ELISPOT assay on peripheral blood mononuclear cells (PBMCS), Th1, Th2, Th3 or balanced Th1/Th2 response will be determined to further characterize the Hp-infected child's immune response phenotype. The investigators propose to further their previous work with critically lacking studies from a multivariate approach, leading to a better understanding of the gastroduodenal disease sequelae and overall pathobiology of Hp infection in humans.


Condition
Helicobacter Infections
Gastritis
Peptic Ulcer

Study Type: Observational
Official Title: Risk Factors for Gastric Disease in Pediatric H. Pylori

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Estimated Enrollment: 755
Study Start Date: October 1997
Study Completion Date: December 2007
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   6 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Using the power determinations for age, gender and demographic characteristics, the investigators will screen all patients undergoing diagnostic upper endoscopy at:

    • Children's Healthcare of Atlanta (Egleston and Scottish Rite Children's Hospitals), Atlanta, GA
    • Rainbow Babies and Children's Hospital, Cleveland, OH
    • Miami Children's Hospital, Miami, FL.
  • Patients will be enrolled over the first 3 years of the study, and then based on interim univariate analysis. The investigators also will perform follow-up evaluations (i.e., clinically-indicated) on the two novel cohorts identified during the first 5 years of funding:

    • the atrophic gastritis Hp-infected cohort
    • the esophagitis/gastritis cohort, in order to assess the natural history of gastroduodenal inflammation in the Hp-infected child.

Exclusion Criteria:

  • Patients who have taken antibiotics within one month of endoscopy will be excluded, as preceding antibiotic therapy will confound ability to determine Hp infection status.
  • In the previous five years, the investigators initially eliminated children taking proton pump inhibitors (PPIs) (e.g., omeprazole); Na+/H+ ATPase channel inhibitors. PPIs have a minimum inhibitory concentration (MIC) against Hp in vitro, and therefore may reduce the overall bacterial load, diminishing the ability to detect infection, and resolve gastroduodenal mucosal inflammation, confounding characterization of cellular host response to Hp infection. However, due to the pervasive use of PPIs in the pediatric population, and the exclusion of potential cases, the investigators improved their culture sensitivity techniques and are able to successfully detect the organism in the setting of a child on a PPI. This will be taken into account when characterizing the gastric mucosal inflammatory phenotype and comparative analyses are performed.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00212225

Locations
United States, Florida
Miami Children's Hospital; Division of Pediatric Gastroenterology
Miami, Florida, United States, 33105
United States, Georgia
Emory University School of Medicine; Emory Children's Center
Atlanta, Georgia, United States, 30322
United States, Ohio
Case Western Reserve University; Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Investigators
Principal Investigator: Benjamin D. Gold, M.D. Emory University
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00212225     History of Changes
Other Study ID Numbers: DK53708 (completed)
Study First Received: September 20, 2005
Last Updated: January 12, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
gastric disease
H. pylori
children
Helicobacter pylori
child
epidemiology

Additional relevant MeSH terms:
Helicobacter Infections
Peptic Ulcer
Stomach Diseases
Bacterial Infections
Digestive System Diseases
Duodenal Diseases
Gastrointestinal Diseases
Gram-Negative Bacterial Infections
Intestinal Diseases

ClinicalTrials.gov processed this record on November 20, 2014