Identification/Characterization of Changes in Microscopic Colitis

August 31, 2021 updated by: Hamed Khalili, Massachusetts General Hospital

Identification and Characterization of Microbial and Immunologic Changes in Microscopic Colitis

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.

Study Overview

Status

Recruiting

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Anticipated)

330

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Hamed Khalili, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with suspected or established microscopic colitis who are scheduled to receive a diagnostic colonoscopy or attend an office visit at the MGH Gastroenterology Unit will be eligible for recruitment

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Microscopic Colitis
Patients with confirmed microscopic colitis
Control
Patients that are not diagnosed with microscopic colitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1.5 years
Immune Response
Time Frame: 1.5 years
Immune cells in blood and biopsy samples will be sorted and quantified using flow cytometry
1.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Takeda Pharmaceuticals North America, Inc.
American College of Gastroenterology

Investigators

  • Principal Investigator: Hamed Khalili, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2015

Primary Completion (Anticipated)

July 31, 2023

Study Completion (Anticipated)

January 31, 2024

Study Registration Dates

First Submitted

February 21, 2017

First Submitted That Met QC Criteria

February 21, 2017

First Posted (Actual)

February 24, 2017

Study Record Updates

Last Update Posted (Actual)

September 1, 2021

Last Update Submitted That Met QC Criteria

August 31, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015P001333

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Only de-identified information may be shared with other collaborators and entities involved in generating data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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