Identification/Characterization of Changes in Microscopic Colitis

NCT ID: NCT03063957

Last Updated: 2021-09-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

330 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-06-30

Study Completion Date

2024-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Colitis, Microscopic

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Microscopic Colitis

Patients with confirmed microscopic colitis

No interventions assigned to this group

Control

Patients that are not diagnosed with microscopic colitis

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda Pharmaceuticals North America, Inc.

INDUSTRY

Sponsor Role collaborator

American College of Gastroenterology

OTHER

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Hamed Khalili

Assistant Professor of Medicine at Harvard Medical School

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hamed Khalili, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Hamed Khalili, MD

Role: CONTACT

978-882-6709

Facility Contacts

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Lauren Canha

Role: primary

617-724-1688

Katie Williams

Role: backup

617-643-9374

References

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

Reference Type BACKGROUND
PMID: 23419063 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19098875 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25997458 (View on PubMed)

Jarnerot G, Hertervig E, Granno C, Thorhallsson E, Eriksson S, Tysk C, Hansson I, Bjorknas H, Bohr J, Olesen M, Willen R, Kagevi I, Danielsson A. Familial occurrence of microscopic colitis: a report on five families. Scand J Gastroenterol. 2001 Sep;36(9):959-62. doi: 10.1080/003655201750305486.

Reference Type BACKGROUND
PMID: 11521987 (View on PubMed)

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. doi: 10.3748/wjg.15.3122.

Reference Type BACKGROUND
PMID: 19575491 (View on PubMed)

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. doi: 10.1023/a:1005593628991. No abstract available.

Reference Type BACKGROUND
PMID: 10795766 (View on PubMed)

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. doi: 10.1097/01.mcg.0000180634.84689.c2.

Reference Type BACKGROUND
PMID: 16208113 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19136110 (View on PubMed)

Other Identifiers

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2015P001333

Identifier Type: -

Identifier Source: org_study_id

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