The Role of the Pregnane X Receptor (PXR) in Indole Signaling and Intestinal Permeability in Inflammatory Bowel Disease

The goal of this study is to better understand the mechanisms responsible for the development of and the severity of Inflammatory Bowel Disease (IBD), such as Crohn's Disease and Ulcerative Colitis, which cause inflammation of the gut as well as potentially affecting other areas of the body

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Diagnostic test: Stool collection; Diagnostic test: Biopsy collection

Detailed Description

Based on promising preliminary data, the study will characterize the claim that PXR signaling serves as a key mechanistic link between the host environment and the innate immune system in the gut. It is widely believed that one cause of IBD stems from abnormal sensing of commensal bacteria. The research will shed light on the molecular mechanisms used by gut barrier epithelial cells in sensing commensals and regulating inflammatory responses in the gut. This will provide a new mechanism towards which more mechanisms derived probiotics could be used to abrogate intestinal inflammation. It is hoped that these agents would eventually serve as non-toxic alternatives or adjuncts to currently available therapeutics for IBD. The research protocol will involve the collection of feces, either by self-collection or through colonoscopic washing.

• Study Type: Observational
• Enrollment (Actual): 43

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects belonging to the target population, (i.e., Diagnosed with IBD, specifically Crohn's disease, ulcerative colitis, or indeterminate colitis and patients with no diagnosis of IBD in whom small intestinal, colonic, or ileocolonic resection is recommended.

Description

Inclusion Criteria:

i) IBD patients

• Patients aged 18-65 with a diagnosis of Crohn's disease, ulcerative colitis, or indeterminate colitis
• Willing and able to consent to participation in study
• In order to enroll in complete study, a clear indication for colonoscopy must be present. If colonoscopy is not indicated, patients may elect to participate by providing a stool specimen without undergoing colonoscopy.
• IBD patients with a clinical recommendation for small intestinal, colonic, or ileocolonic resection

ii) Control patients

• Patients aged 18-65 with no diagnosis of inflammatory bowel disease being seen in the gastroenterology practice for the following indications

  • Screening colonoscopy
  • Iron deficiency anemia
  • Rectal bleeding
  • Esophageal reflux (colonoscopy only would be done if indicated for other reasons)
  • Diarrhea (with exclusion of inflammatory bowel disease)
• Patients with no diagnosis of inflammatory bowel disease being seen in the surgery practice in whom small intestinal, colonic, or ileocolonic resection is recommended

iii) Pre-existing specimens from IBD patients

• Pre-existing specimens from the IBD patient tissue biobank of Dr. Gitit Tomer will also be analyzed. Only patient samples from patients who have provided informed written consent for use in future studies on the consent form for the pediatric IBD tissue biobank will be utilized in this study. Such patient specimens will be assigned a unique study identifier and the data will be stored as indicated below. There are currently 38 patients within this biobank, of which all 38 provided consent for use of the specimens in future studies. Specimens include both ileal and colonic biopsies, ileal and colonic fecal aspirates, and serum.

iv) Pediatric IBD patients

• Patients aged 0-22 with a diagnosis of Crohn's disease, ulcerative colitis, indeterminate colitis, or a family history of IBD
• Willing and able to consent to participation in study, or a parent or guardian provides written consent for participation
• In order to enroll in the complete study, a clear indication for colonoscopy and biopsy must be present. If colonoscopy is not indicated, patients may elect to participate by providing a stool specimen without undergoing colonoscopy.
• Pediatric IBD patients with a clinical recommendation for small intestinal, colonic, or ileocolonic resection

Exclusion Criteria:

• Unwilling or unable to provide consent
• Presence of comorbid systemic inflammatory disorders such as rheumatoid arthritis, sarcoidosis, psoriasis, multiple sclerosis, advanced or decompensated heart failure, cirrhosis, or morbid obesity (Body mass index (BMI) over 40)
• Irritable bowel syndrome
• Bowel obstruction
• Contraindication to colonoscopy or biopsies
• Cancer or malignancy within 12 months

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Inflammatory Bowel Disease (IBD); Subjects will be asked to provide a stool sample (if no colonoscopy is to be performed) or if clinically indicated, a colonoscopy will be performed per standard medical routine. During colonoscopy, stool will be collected for analysis and 3 additional biopsies will be taken each from the ileum and colon for research purposes. Alternatively, subjects who are undergoing intestinal and/or colonic resection will provide stool prior to surgery and a portion of their pathology specimens will be used for research purposes following complete pathologic evaluation.	Diagnostic test: Stool collection; Stool will be collected from subjects who have been diagnosed with IBD or whom small intestinal, colonic or ileocolonic and have signed consent for the control group. Stool will be self-collected or through routine colonoscopy procedure.; Diagnostic test: Biopsy collection; 3 additional biopsies (for research purposes) will be taken from patients who undergo colonoscopy as per standard of care
Subjects not affected by IBD (Control Group); Results of subjects with IBD will be compared to subjects in the control group.	Diagnostic test: Stool collection; Stool will be collected from subjects who have been diagnosed with IBD or whom small intestinal, colonic or ileocolonic and have signed consent for the control group. Stool will be self-collected or through routine colonoscopy procedure.; Diagnostic test: Biopsy collection; 3 additional biopsies (for research purposes) will be taken from patients who undergo colonoscopy as per standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of molecular studies in subjects with and without IBD	We will measure and analyze RNA and protein levels of cytokines, junctional protein expression, PXR (pregnane X receptor) and TLRs (toll-like receptors) in tissues and perform intestinal permeability studies in subjects with and without IBD.	Up to 5 years
Assays for biofilm and phage		Up to 5 years

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sridhar Mani, MD, Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2015
• Primary Completion (Actual): May 2, 2019
• Study Completion (Actual): May 2, 2019

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): September 16, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: 2015-4465; 3R01CA127231 (U.S. NIH Grant/Contract); 5R01CA161879 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No