The Role of the Pregnane X Receptor (PXR) in Indole Signaling and Intestinal Permeability in Inflammatory Bowel Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Analysis of molecular studies in subjects with and without IBD
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Analysis of molecular studies in subjects with and without IBD
时间窗: Up to 5 years
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.
Assays for biofilm and phage
时间窗: Up to 5 years
次要结局
未报告次要终点
研究者
Sridhar Mani
Principal Investigator
Albert Einstein College of Medicine