Brief Summary
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
Brief Title
The Role of the Pregnane X Receptor (PXR) in Indole Signaling and Intestinal Permeability in Inflammatory Bowel Disease
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Inflammatory Bowel Diseases
Eligibility Criteria
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
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
Inclusion Criteria
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
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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
65 Years
NCT Id
NCT04089501
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2015-4465
Overall Status
Completed
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
The Role of the Pregnane X Receptor (PXR) in Indole Signaling and Intestinal Permeability in Inflammatory Bowel Disease
Primary Outcomes
Outcome Description
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.
Outcome Measure
Analysis of molecular studies in subjects with and without IBD
Outcome Time Frame
Up to 5 years
Outcome Measure
Assays for biofilm and phage
Outcome Time Frame
Up to 5 years
Secondary Ids
Secondary Id
3R01CA127231
Secondary Id
5R01CA161879
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
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.
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
65
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Olga Aroniadis
Investigator Email
oaroniad@montefiore.org
Investigator Phone
Categories Mesh Debug
Digestive System --- INFLAMMATORY BOWEL DISEASES
Digestive System --- GASTROENTERITIS
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL DISEASES
Digestive System --- GASTROINTESTINAL DISEASES
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Gastrointestinal (GI) Cancers --- INTESTINAL DISEASES
Digestive System --- INTESTINAL DISEASES
MeSH Terms
INFLAMMATORY BOWEL DISEASES
GASTROENTERITIS
GASTROINTESTINAL DISEASES
DIGESTIVE SYSTEM DISEASES
INTESTINAL DISEASES