Colitis, MicroscopicNCT03063957
Identification/Characterization of Changes in Microscopic Colitis
An observational study of Colitis, Microscopic, run by Massachusetts General Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colitis, Microscopic
- How many people
- 330 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jun 2015to 31 Jan 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Lauren Canha, 617-724-1688, lcanha@partners.org
Katie Williams, 617-643-9374, kwilliams81@partners.org
About this study
Official title: 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.
Read the 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.
- Conditions
- Colitis, Microscopic
- Medical subject headings
- Colitis, Microscopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Microscopic Colitis | Patients with confirmed microscopic colitis | |
| Control | Patients that are not diagnosed with microscopic colitis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microbiome Analysis
Standard 16s rRNA sequencing for taxonomic identification and metagenomic profiling of the gut microbiome will be performed on stool and tissue samples.
Measured: 1.5 years
Immune Response
Immune cells in blood and biopsy samples will be sorted and quantified using flow cytometry
Measured: 1.5 years
Secondary outcomes (1)
α4β7 in microscopic colitis pathogenesis
Vedolizumab will be used as a reagent for in vitro identification and investigation of eosinophils that express α4β7
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2017
- Study start30 Jun 2015
- Primary completion31 Jul 2023 (estimated)
- Study completion31 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Colitis, MicroscopicStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 330 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda Pharmaceuticals North America, Inc., American College of Gastroenterology
- Responsible party
- Principal investigator, Hamed Khalili, Massachusetts General Hospital
- Investigators
- Hamed Khalili, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03063957
- Sponsor's protocol ID
- 2015P001333
- Status last verified
- Aug 2021
- First submitted
- 21 Feb 2017
- Last updated
- 1 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Only de-identified information may be shared with other collaborators and entities involved in generating data.
Publications
Brown WR, Tayal S. Microscopic colitis. A review. J Dig Dis. 2013 Jun;14(6):277-81. doi: 10.1111/1751-2980.12046.
PubMed 23419063Chande 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.
PubMed 19098875Colussi 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.
PubMed 25997458Jarnerot 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.
PubMed 11521987Kao 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.
PubMed 19575491Khan 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.
PubMed 10795766LaSala 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.
PubMed 16208113Yao 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.
PubMed 19136110
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification and Characterization of Microbial and Immunologic Changes in Microscopic Colitis
- ClinicalTrials.gov ID
- NCT03063957
- Acronym / sponsor ID
- 2015P001333
- Conditions
- Colitis, Microscopic
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 330 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Takeda Pharmaceuticals North America, Inc., American College of Gastroenterology
- Study start
- 30 Jun 2015 (actual)
- Primary completion
- 31 Jul 2023 (estimated)
- Study completion
- 31 Jan 2024 (estimated)
- First posted
- 24 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Microscopic Colitis | – | –Patients with confirmed microscopic colitis |
| Control | – | –Patients that are not diagnosed with microscopic colitis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
1 secondary outcome
α4β7 in microscopic colitis pathogenesis
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2021.
- Background: PubMed 23419063Brown WR, Tayal S. Microscopic colitis. A review. J Dig Dis. 2013 Jun;14(6):277-81. doi: 10.1111/1751-2980.12046.
- Background: PubMed 19098875Chande 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.
- Background: PubMed 25997458Colussi 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.
- Background: PubMed 11521987Jarnerot 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.
- Background: PubMed 19575491Kao 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.
- Background: PubMed 10795766Khan 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.
- Background: PubMed 16208113LaSala 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.
- Background: PubMed 19136110Yao 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.
- Individual participant dataSharing planned: No. Only de-identified information may be shared with other collaborators and entities involved in generating data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hamed Khalili, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colitis, Microscopic, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hamed Khalili, MD (978-882-6709, hkhalili@partners.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Microbiome Analysis (time frame: 1.5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03063957, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2021.