The Role of Intestinal Inflammation in Irritable Bowel Syndrome (IBS) (K23)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Yehuda Ringel, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01072903
First received: February 18, 2010
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

The research project addresses the following hypotheses (A) the normal balance of beneficial and detrimental commensal intestinal bacteria is deranged in IBS, with selective alterations in clinically defined patient subsets i.e., diarrhea predominant IBS (D-IBS) and post-infectious IBS (PI-IBS); (B) these changes in intestinal microflora are associated with sub-clinical mucosal inflammation and activation of the mucosal immune system; and (C) activation of the mucosal immune system leads to alterations in gastrointestinal (GI) functions (i.e., motility and sensation) and functional symptoms.


Condition
Inflammation
Colon, Irritable
Colonic Diseases, Functional
Irritable Bowel Syndrome

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: The Role of Intestinal Inflammation in the Pathophysiology of IBS

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Biospecimen Retention:   Samples Without DNA

8 rectosigmoidal intestinal biopsies, stool, and blood


Enrollment: 78
Study Start Date: January 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
IBS
Subjects with IBS
Healthy
Healthy Controls

Detailed Description:

There are two main aims in the research study. The first aim is to determine whether sub-clinical mucosal inflammation occurs in patients with D-IBS by identifying alterations in mucosal markers for inflammation (inflammatory cytokines and inflammation-related mediators). The second aim is to investigate whether the identifiable alterations in inflammatory markers are associated with specific abnormalities in intestinal motor and sensory functions that are relevant to the pathophysiology of IBS.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

This research plans to study 33 diarrhea predominant Irritable Bowel Syndrome and IBS-mixed/alternators patients with current symptom activity (abdominal pain at least once a week in the past month) and 33 healthy controls. The subjects will be of any gender, race or ethnicity and at least 18 years of age. Recruitment for the proposed study takes advantage of an ongoing NIH-supported research study on the heterogeneity of IBS (NIDDK Grant DK 31369, WE Whitehead - PI, IRB#01-1397, GCRC# 1846) currently conducted at UNC.

Criteria

Inclusion Criteria:

  • Any sex, race, or ethnicity.
  • At least 18 years of age (no upper age limit).
  • D-IBS and M-IBS patients must meet Rome II criteria for IBS and must have been evaluated by a physician to exclude alternative diseases that could explain the symptoms. For the latter, patients' self statement is acceptable (by self-report, no official document is required).
  • D-IBS and M-IBS subjects older than 50 years old must have had a colonoscopy in the past 5 years with a normal report. Hemorrhoids, diverticulosis and polyps are allowed.
  • Participation in Dr. Whitehead's heterogeneity of IBS research study, or Dr. Ringel's Probiotic Pain Study.

Exclusion Criteria:

  • Healthy controls must have no significant or recurring gastrointestinal symptoms.
  • Patients and healthy controls should not have a serious, unstable medical condition.
  • Patients and healthy controls must have had no gastrointestinal tract surgery other than appendectomy or cholecystectomy, or any abdominal surgery within the past 3 months. Appendectomy and cholecystectomy are allowed if done more than 2 years ago and symptoms were not changed following the surgery.
  • Pregnancy and breastfeeding (by self-report).
  • No history of inflammatory bowel diseases, celiac disease, or other diagnosis that could explain chronic or recurring bowel symptoms in IBS patients or controls (by self-report).
  • Patients and controls should have no history of lactose malabsorption (by self-report).
  • Patients and controls should have no history of clinical symptoms of acute infections during the last 8 weeks prior to enrollment in the study.
  • Patients and controls should have no history of anti-inflammatory agents including aspirin, non-aspirin, non-steroid anti-inflammatory (NSAID), steroids, antibiotic, or probiotics treatment during the last 4 weeks prior to enrollment in the study.
  • Patients should not have an implanted or portable electro-mechanical medical device such as a pacemaker and/or other implanted stimulators or pumps.
  • Evidence of acute inflammation on routine histology.
  • Evidence of enteric pathogens on routine stool cultures.
  • Presence of a medical condition that requires routine use of antibiotic treatment with dental or other invasive procedures (by self-report).
  • To be confirmed at time of screening and the week of the flexible sigmoidoscopy appointment for IBS-M subjects ONLY: In the past week, subject cannot have less than 3 (0-2) bowel movements. Also, in the past week, subject cannot have hard/lumpy stools for 2 or more days.

Only subjects with IBS may participate in the optional SmartPill testing. Subjects are excluded from SmartPill testing if a subject has:

  • A history of gastric bezoar.
  • Suspected strictures, fistulas, colon cancer or other physiological GI obstruction.
  • Dysphagia.
  • Diverticulitis.
  • Tobacco use within eight hours prior to capsule ingestion and during the initial 8 hour recording on Day 0 or the Ingestion visit.
  • Alcohol use within eight hours prior to capsule ingestion and throughout the entire monitoring period (5 days).
  • Body Mass Index > 40 kg/m2.
  • Female of childbearing age who is not practicing birth control and/or are pregnant or lactating.
  • Cardiovascular, endocrine, renal, or other chronic disease likely to affect motility.
  • A medical device such as a pacemaker, infusion pump, or insulin pump.
  • Any contraindication to use of Fleets Enema or the balloon expulsion test.
  • Uncontrolled diabetes with a hemoglobin A1C greater than 10.
  • Allergies to any of the ingredients of the standard SmartBar meal
  • Subject plans to take any of the following prohibited medications: Medication to alter gastric pH, Medication that affect GI motility for 3 full days before the start of the study and during the ensuing days of study, Medication for nausea and vomiting that block serotonin receptors, Anti-diarrheal agents, Opiate agents used to treat diarrhea, Non-steroidal anti-inflammatory drugs
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01072903

Locations
United States, North Carolina
University of North Carolina at Chapel Hill, Program in Digestive Health and the Department of Gastroenterology and Hepatology
Chapel Hill, North Carolina, United States, 27599-7080
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Yehuda Ringel, MD UNC Chapel Hill Department of Gastroenterology and Hepatology
  More Information

Publications:
Responsible Party: Yehuda Ringel, Associate Professor of Medicine, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01072903     History of Changes
Other Study ID Numbers: 08-1106, K23DK075621
Study First Received: February 18, 2010
Last Updated: December 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
inflammation
colon, irritable
Colonic Diseases, Functional
Irritable Bowel Syndrome

Additional relevant MeSH terms:
Colonic Diseases
Colonic Diseases, Functional
Inflammation
Irritable Bowel Syndrome
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 31, 2014