Identification/Characterization of Changes in Microscopic Colitis

Colitis, Microscopic Clinical Trial

Official title:

Identification and Characterization of Microbial and Immunologic Changes in Microscopic Colitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03063957
• Other study ID #: 2015P001333
• Status: Recruiting
• Start date: June 30, 2015
• Est. completion date: January 31, 2024

Study information

• Verified date: August 2021
• Source: Massachusetts General Hospital
• Contact: Hamed Khalili, MD
• Phone: 978-882-6709
• Email: hkhalili[@]partners.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this study is to establish a prospective observational cohort of adult patients with microscopic colitis and collect clinical information and specimens over the course of their treatment. This information will be used in order to establish a patient registry with detailed clinical data and a specimen repository for future research as well as to specifically identify genetic and molecular characteristics associated with microscopic colitis.

Description:

Microscopic colitis (MC) is a chronic relapsing disease of the colon, characterized by watery non-bloody diarrhea, usually normal colonoscopic findings, and typical histology findings. It is frequently accompanied by abdominal pain, nocturnal diarrhea, and mild weight loss. The incidence of MC has increased significantly over recent years with a 2010 study reporting U.S. incidence for MC as 19.7 per 100,000 person-years. MC comprises two major histological subtypes: collagenous colitis (CC), characterized by a distinctive thickened band of subepithelial collagen (>10-20um), and lymphocytic colitis (LC), with an increased number of intraepithelial lymphocytes (>20 lymphocytes per 100 epithelial cells).

Although the exact etiology of MC remains largely unknown, a few observational studies have suggested associations with autoimmune disorders (e.g. celiac disease, and thyroid disorders), cigarette smoking status, and medications such as non-steroidal anti-inflammatory drugs (NSAIDS), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRI), and statins. In addition to environmental factors, recently studies indicate that genetics and specific infectious organisms may also play a role in development of the disease. A recent study revealed a seasonal incidence pattern of lymphocytic colitis, suggesting a potential link to an infectious or allergic component. Further, one study demonstrated an association between collagenous colitis and persistent colonic C. difficile infection. Additionally, while familial occurrence of MC has been reported, suggesting a genetic predisposition, the roles of specific genetic factors have not been described. Finally, recent studies demonstrate an association between MC and various autoimmune disorders including celiac disease, autoimmune thyroid disease, and Sjören's syndrome, indicating that MC may be part of a broader spectrum of autoimmune disorders. Despite these findings, few studies have investigated the role of genetic, infectious, and immunological factors in the development and progression of MC.

Budesonide is the only treatment for MC that appeared to be effective in randomized controlled trials, with remission rates of 80%. However, recurrence of clinical symptoms following withdrawal of treatment is not uncommon. Thus, further investigation of the molecular mechanisms underlying MC is needed in order to obtain targeted and sustainable treatment.

Analysis of clinical specimens obtained by colonoscopy from individuals affected with MC over the course of their treatment offers a promising method by which to improve our understanding of MC. Profiling of genetic and molecular characteristics such as changes in gut flora, colonic mucosal immune profiles, and genetic factors over the course of treatment would provide powerful insight into the role of these factors in the pathophysiology of the disease which may ultimately lead to better treatments. Additionally, identification of disease biomarkers can aid in developing disease monitoring and surveillance strategies.

Here, we propose to establish a cohort of individuals with suspected microscopic colitis undergoing diagnostic colonoscopy at the Massachusetts General Hospital (MGH) to identify genetic and molecular characteristics associated with the progression of this disease. This study will elaborate on findings from a medical record review of patients with microscopic colitis treated at MGH from 2002 to 2014. In addition to medical records, genetic and molecular characteristics of colonic samples will be examined to determine their influence on treatment response and outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 330
• Est. completion date: January 31, 2024
• Est. primary completion date: July 31, 2023
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ability to give informed consent

• Ability and willingness to comply with all patient visits and study-related procedures

• Ability to understand and complete all study-related materials and questionnaires

• Patients ages 18 or older with suspected microscopic colitis

• Patients that have been previously treated for microscopic colitis that are being seen for possible relapse will also be included

Exclusion Criteria:

• Inability to provide informed consent

• Inability or unwillingness to comply with all patient visits and study-related procedures

• Inability to understand and complete all study-related materials and questionnaires

• Patients with a known diagnosis of Inflammatory Bowel Disease or colorectal cancer

• Patients with a known bleeding disorder, acute disease, or those that are awaiting transplantation

• Patients who have taken antibiotics in the last two weeks

• Female subjects who are pregnant or nursing

Related Conditions & MeSH terms

• Colitis
• Colitis, Microscopic

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Massachusetts General Hospital	American College of Gastroenterology, Takeda Pharmaceuticals North America, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (8)

Brown WR, Tayal S. Microscopic colitis. A review. J Dig Dis. 2013 Jun;14(6):277-81. doi: 10.1111/1751-2980.12046. Review. — View Citation

Chande N, MacDonald JK, McDonald JW. Interventions for treating microscopic colitis: a Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group systematic review of randomized trials. Am J Gastroenterol. 2009 Jan;104(1):235-41; quiz 234, 242. doi: 10.1038/ajg.2008.16. Review. — View Citation

Colussi D, Salari B, Stewart KO, Lauwers GY, Richter JR, Chan AT, Ricciardiello L, Khalili H. Clinical characteristics and patterns and predictors of response to therapy in collagenous and lymphocytic colitis. Scand J Gastroenterol. 2015;50(11):1382-8. doi: 10.3109/00365521.2015.1050692. Epub 2015 May 21. — View Citation

Järnerot G, Hertervig E, Grännö C, Thorhallsson E, Eriksson S, Tysk C, Hansson I, Björknäs H, Bohr J, Olesen M, Willén R, Kagevi I, Danielsson A. Familial occurrence of microscopic colitis: a report on five families. Scand J Gastroenterol. 2001 Sep;36(9):959-62. — View Citation

Kao KT, Pedraza BA, McClune AC, Rios DA, Mao YQ, Zuch RH, Kanter MH, Wirio S, Conteas CN. Microscopic colitis: a large retrospective analysis from a health maintenance organization experience. World J Gastroenterol. 2009 Jul 7;15(25):3122-7. — View Citation

Khan MA, Brunt EM, Longo WE, Presti ME. Persistent Clostridium difficile colitis: a possible etiology for the development of collagenous colitis. Dig Dis Sci. 2000 May;45(5):998-1001. — View Citation

LaSala PR, Chodosh AB, Vecchio JA, Schned LM, Blaszyk H. Seasonal pattern of onset in lymphocytic colitis. J Clin Gastroenterol. 2005 Nov-Dec;39(10):891-3. — View Citation

Yao MD, von Rosenvinge EC, Groden C, Mannon PJ. Multiple endoscopic biopsies in research subjects: safety results from a National Institutes of Health series. Gastrointest Endosc. 2009 Apr;69(4):906-10. doi: 10.1016/j.gie.2008.05.015. Epub 2009 Jan 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbiome Analysis	Standard 16s rRNA sequencing for taxonomic identification and metagenomic profiling of the gut microbiome will be performed on stool and tissue samples.	1.5 years
Primary	Immune Response	Immune cells in blood and biopsy samples will be sorted and quantified using flow cytometry	1.5 years
Secondary	a4ß7 in microscopic colitis pathogenesis	Vedolizumab will be used as a reagent for in vitro identification and investigation of eosinophils that express a4ß7	2 years