Identification/Characterization of Changes in Microscopic Colitis
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| ClinicalTrials.gov Identifier: NCT03063957 |
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Recruitment Status :
Recruiting
First Posted : February 24, 2017
Last Update Posted : September 1, 2021
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| Condition or disease |
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| Colitis, Microscopic |
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.
| Study Type : | Observational |
| Estimated Enrollment : | 330 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | Identification and Characterization of Microbial and Immunologic Changes in Microscopic Colitis |
| Actual Study Start Date : | June 30, 2015 |
| Estimated Primary Completion Date : | July 31, 2023 |
| Estimated Study Completion Date : | January 31, 2024 |
| Group/Cohort |
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Microscopic Colitis
Patients with confirmed microscopic colitis
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Control
Patients that are not diagnosed with microscopic colitis
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- Microbiome Analysis [ Time Frame: 1.5 years ]Standard 16s rRNA sequencing for taxonomic identification and metagenomic profiling of the gut microbiome will be performed on stool and tissue samples.
- Immune Response [ Time Frame: 1.5 years ]Immune cells in blood and biopsy samples will be sorted and quantified using flow cytometry
- α4β7 in microscopic colitis pathogenesis [ Time Frame: 2 years ]Vedolizumab will be used as a reagent for in vitro identification and investigation of eosinophils that express α4β7
Biospecimen Retention: Samples With DNA
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Sampling Method: | Non-Probability Sample |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03063957
| Contact: Hamed Khalili, MD | 978-882-6709 | hkhalili@partners.org |
| United States, Massachusetts | |
| Massachusetts General Hospital | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: Lauren Canha 617-724-1688 lcanha@partners.org | |
| Contact: Katie Williams 617-643-9374 kwilliams81@partners.org | |
| Principal Investigator: Hamed Khalili, MD | |
| Principal Investigator: | Hamed Khalili, MD | Massachusetts General Hospital |
| Responsible Party: | Hamed Khalili, Assistant Professor of Medicine at Harvard Medical School, Massachusetts General Hospital |
| ClinicalTrials.gov Identifier: | NCT03063957 |
| Other Study ID Numbers: |
2015P001333 |
| First Posted: | February 24, 2017 Key Record Dates |
| Last Update Posted: | September 1, 2021 |
| Last Verified: | August 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Only de-identified information may be shared with other collaborators and entities involved in generating data. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Colitis Colitis, Microscopic Gastroenteritis Gastrointestinal Diseases |
Digestive System Diseases Colonic Diseases Intestinal Diseases |