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The Role of CD4+ T Cell Subsets in the Mechanism of Action of Vedolizumab in Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT02721719
Recruitment Status : Recruiting
First Posted : March 29, 2016
Last Update Posted : June 8, 2018
Sponsor:
Information provided by (Responsible Party):
Brian Bressler, University of British Columbia

Brief Summary:

The cause of Inflammatory Bowl Disease (IBD) is not known, but studies from patients with IBD have found that these patients make unusually strong immune responses to their own intestinal tissues and to bacteria that normally live in the healthy gut. These overactive immune responses might result from an imbalance of T-lymphocytes, which are a type of white blood cell that recognize and respond to threats like infection or damaged tissues. In healthy tissues, a type of T-lymphocytes called T-regulatory cells control excess inflammation by preventing other T cells, called T-effector cells from responding. We believe that T-regulatory cells are somehow less active in IBD, resulting in damage to intestinal tissues by the T-effector cells.

T-lymphocytes, including both T-regulatory and T-effector cells, are guided to different parts of the body by 'alpha4beta7-integrin' molecules. Vedolizumab or Entyvio works by blocking this homing molecule so that T cells do not reach the intestine, but stay in the blood where they cannot aggravate your IBD. This study will help in understanding how Vedolizumab helps to heal or decrease the symptoms of your Ulcerative Colitis.

The effect of Vedolizumab on different types of T cells in the human intestine has not yet been studied. However, the investigators think that Vedolizumab will shift the balance of T cells in the intestine towards more healing T-regulatory cells and less damaging T-effector cells. The purpose of this study is to measure the different types of T cells in participants' blood and intestinal tissue before and during Vedolizumab treatment.


Condition or disease
Ulcerative Colitis

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: The Role of CD4+ T Cell Subsets in the Mechanism of Action of Vedolizumab in Ulcerative Colitis
Study Start Date : May 2016
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Vedolizumab

Group/Cohort
Healthy Adults
[Not receiving Vedolizumab] Healthy adults who have not donated blood within the past two months and who have no history of blood-borne diseases.
Adults with no Inflammatory Bowl Disease
[Not receiving Vedolizumab] Adult patients undergoing endoscopy for indications other than Inflammatory Bowel Disease or other inflammatory conditions of the bowel (such as colon cancer screening or polypectomy)
Donors with Ulcerative Colitis
[Set to receive Vedolizumab] Adults with an established diagnosis of UC (≥ 6 months preceding involvement in study) who are both scheduled for an endoscopy and are about to receive Vedolizumab treatment (standard of care).



Primary Outcome Measures :
  1. Differences in CD4+ T cell subsets in the blood and colonic tissue of IBD patients before and after Vedolizumab treatment; relative CD4+ T cell numbers will be determined by immunofluorescent detection of subset specific markers. [ Time Frame: Two years ]

Secondary Outcome Measures :
  1. Differences in the stability of T regulatory cells with and without alpha4beta7 integrin binding as measured by maintenance of the Treg-specific-demethylation region in the FoxP3 promoter. [ Time Frame: Two years ]
  2. Differences in the suppressive capacity of T regulatory cells with and without alpha4beta7 integrin binding as measured by ability to suppress the proliferation of CD4+CD25- T effector cells. [ Time Frame: Two years ]

Biospecimen Retention:   Samples Without DNA
Blood & colonic biopsy tissue


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Group 1: Healthy human volunteers who respond to our advertising poster (put up around CFRI and Vancouver General Hospital).

Group 2: Patients who are undergoing endoscopy at the Pacific Gastroenterology Associate's endoscopy clinic for indications other than Inflammatory Bowel Disease (such as colon cancer screening or polypectomy).

Group 3: Participants who are about to undergo Vedolizumab treatment from Pacific Gastroenterology Associate's clinic (affiliated with St. Paul's Hospital) as part of their standard of care treatment. Physicians will identify these patients when they undergo medical consultation for treatment of their Ulcerative Colitis.

Criteria

Inclusion Criteria:

  • Group 1: Healthy adults who have not donated blood within the past two months and who have no history of blood-borne diseases.
  • Group 2: Adult patients undergoing endoscopy for indications other than Inflammatory Bowel Disease or other inflammatory conditions of the bowel (such as colon cancer screening or polypectomy)
  • Group 3: Adults with an established diagnosis of Ulcerative Colitis (≥ 6 months preceding involvement in study) who are both scheduled for an endoscopy and are about to receive Vedolizumab as part of their standard of care treatment. Former anti-TNF treated Ulcerative Colitis patients will not be excluded, however, only 50% of the group 3 patient cohort can be on anti-TNF medications 12 weeks before Vedolizumab initiation.

Exclusion Criteria:

  • Less than 19 years of age or greater than 80 years of age
  • Known or suspected inflammatory conditions of the bowel (such as irritable bowel syndrome, celiac disease)
  • Known or suspected transmissible infectious disease such as HIV, Hep B or C or a hemorrhagic disorder
  • Known hematologic malignancy
  • Pregnancy

Information from the National Library of Medicine

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): NCT02721719


Contacts
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Contact: Amy Wong, BSc 778 588 6700 ext 111 amywonggiresearch@gmail.com
Contact: Maria Ancheta-Schmit, RN, BSN 604 688 6332 ext 235 maria.a.schmit@gmail.com

Locations
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Canada, British Columbia
Child and Family Research Institute Recruiting
Vancouver, British Columbia, Canada, V5Z4H4
Contact: Sabine Ivison, PhD    604 875 2000 ext 6425    sabine.ivison@ubc.ca   
Principal Investigator: Megan Levings, PhD         
Sponsors and Collaborators
University of British Columbia
Investigators
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Principal Investigator: Brian Bressler, MD, FCRP(C) University of British Columbia

Publications:

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Responsible Party: Brian Bressler, Clinical Assistant Professor, University of British Columbia
ClinicalTrials.gov Identifier: NCT02721719     History of Changes
Other Study ID Numbers: H15-01034
First Posted: March 29, 2016    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Brian Bressler, University of British Columbia:
Ulcerative Colitis
UC
Vedolizumab
Entyvio
Inflammatory Bowl Disease
IBD
T-Lymphocytes, Regulatory
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Vedolizumab
Gastrointestinal Agents