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

NCT02721719 | Active Not Recruiting

• 1 other identifier: H15-01034
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; UC; Vedolizumab; Entyvio; Inflammatory Bowl Disease; IBD; T-Lymphocytes, Regulatory

Outcome Measures

Primary Outcomes (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.

  Two years

Secondary Outcomes (2)

• 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.

  Two years

• 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.

  Two years

Study Arms (3)

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).

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

Child and Family Research Institute

Vancouver, British Columbia, V5Z4H4, Canada

Location

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood \& colonic biopsy tissue

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Brian Bressler, MD, FCRP(C)

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 29, 2016
• Study Start: May 1, 2016
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: May 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)