Ulcerative ColitisNCT02721719
The Role of CD4+ T Cell Subsets in the Mechanism of Action of Vedolizumab in Ulcerative Colitis
An observational study of Ulcerative Colitis, run by University of British Columbia at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Ulcerative Colitis
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- May 2016to Dec 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 19 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Child and Family Research Institute
Vancouver, British Columbia, V5Z4H4
About this study
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.
Read the detailed description
Inflammatory bowel disease (IBD) is an umbrella term for Crohn's disease and Ulcerative Colitis (UC), which are thought to be caused by disruption of the intestinal epithelial cell barrier, leading to changes in the intestinal flora and a consequent aberrant activation of the mucosal immune system. The resulting chronic intestinal inflammation is highly dependent on different subsets of CD4+ T helper (Th) cells. For example, correlative data suggest that Crohn's disease is driven by exaggerated Th1 and Th17 cell responses, since inflamed lesions contain increased levels of cytokines associated with these cells including IFNγ, IL-12, and IL-17 and IL-18. In contrast, although Ulcerative Colitis is in the same family of diseases, it is typically associated with Th2 cells since patients have high levels of IL-13 in the intestinal mucosa compared to patients with Crohn's disease or healthy individuals. Recent evidence implicates the newly emerging Th9 subset of Th cells in the pathology of UC. The development and function of Th cells with pathogenic potential is kept in check by another subset of CD4+ T cells, which is known as the regulatory T cell, or Treg. In healthy individuals, the intestinal lamina propria has a large proportion of Tregs, and evidence that simply lacking Tregs leads to IBD, suggests Tregs have a critical role in controlling intestinal homeostasis. Indeed, work in animal models and early phase clinical trials have shown that restoration of Treg function can ameliorate IBD. These data suggest that effective therapies need to promote the function of Tregs. Hence in order to understand the mechanism of action of new therapeutics it is critical to assess their impact on the balance between effector and regulatory CD4+ T cells.
Homing of effector and regulatory T cells to the intestine is controlled by a variety of integrins and chemokine receptors, with evidence that expression of alpha4beta7-integrin molecules (α4β7) on T cells has a key role in this process. Since Vedolizumab (Entyvio) specifically blocks the interaction between α4β7 and its ligands, which are expressed in mucosal tissue, its therapeutic effects in IBD are presumed to be related to a reduction in T cell trafficking to the intestine. However, how this biologic agent specifically affects the homing of Tregs versus effector T cells is unknown. In humans, Tregs in the peripheral blood are reported to express lower levels of α4β7 compared to effector T cells, but the relative expression on different subsets (i.e. Th1, vs. Th2, vs. Th17) of CD4+ T cells is unknown. Interestingly, in the intestine there is also a subset of Tregs that produces IL-17 and expresses high levels of α4β7, but the functional relevance of these cells in IBD is unknown. In addition, in mice, expression of α4β7 on CD4+ T cells is unstable under inflammatory conditions, suggesting that studies with circulating T cells in healthy individuals may not accurately reflect integrin expression in states of inflammation. Understanding how Vedolizumab affects the localization of circulating versus tissue-localized subsets of CD4+ T cells is key to understanding how this therapy works.
Also unknown is how signaling by α4β7 affects the development and/or function of different subsets of CD4+ T cells. In T cells, integrins not only mediate homing, but they also provide tissue-specific signals. For example, they can act as costimulatory molecules 10-12 and influence cytokine production. The molecular basis for the effects on T cells has not been well characterized, but in other cells integrins activate the PI3K pathway, providing a pro-survival signal 16. Since we have shown that activation of the PI3K pathway regulates the balance of effector versus regulatory T cells 17, it is possible that blockade of α4β7 may reduce PI3K signaling and favor the development of Tregs. In support of this possibility, we have shown that fibronectin, which is a ligand for α4β7, inhibits the development of Tregs.
This is an observational study to determine the expression pattern and function of α4β7 on effector and regulatory CD4+ T cells, and to define how treatment with Vedolizumab affects the homing and function of these cells. We hypothesize that that treatment with Vedolizumab will shift the balance of effector and regulatory T cells through two mechanisms: 1) altered migration of different subsets of CD4+ T cells to the intestine; and 2) promoting Treg stability as a consequence of reduced PI3K signaling downstream of α4β7.
- Conditions
- Ulcerative Colitis
- Keywords
- Ulcerative Colitis, UC, Vedolizumab, Entyvio, Inflammatory Bowl Disease, IBD, T-Lymphocytes, Regulatory
- Medical subject headings
- Colitis, Ulcerative
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 |
|---|---|---|
| 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2016 (estimated)
- Study startMay 2016
- Primary completionDec 2023
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (31)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Bressler, University of British Columbia
- Investigators
- Brian Bressler, MD, FCRP(C), Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02721719
- Sponsor's protocol ID
- H15-01034
- Status last verified
- May 2024
- First submitted
- 8 Mar 2016
- Last updated
- 17 May 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hardenberg G, Steiner TS, Levings MK. Environmental influences on T regulatory cells in inflammatory bowel disease. Semin Immunol. 2011 Apr;23(2):130-8. doi: 10.1016/j.smim.2011.01.012. Epub 2011 Feb 3.
PubMed 21295492Mallone R, Mannering SI, Brooks-Worrell BM, Durinovic-Bello I, Cilio CM, Wong FS, Schloot NC; T-Cell Workshop Committee, Immunology of Diabetes Society. Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society. Clin Exp Immunol. 2011 Jan;163(1):33-49. doi: 10.1111/j.1365-2249.2010.04272.x. Epub 2010 Oct 5.
PubMed 20939860Nalleweg N, Chiriac MT, Podstawa E, Lehmann C, Rau TT, Atreya R, Krauss E, Hundorfean G, Fichtner-Feigl S, Hartmann A, Becker C, Mudter J. IL-9 and its receptor are predominantly involved in the pathogenesis of UC. Gut. 2015 May;64(5):743-55. doi: 10.1136/gutjnl-2013-305947. Epub 2014 Jun 23.
PubMed 24957265Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001 Nov;22(11):633-40. doi: 10.1016/s1471-4906(01)02060-9.
PubMed 11698225Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER. The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9.
PubMed 19509315Iellem A, Colantonio L, D'Ambrosio D. Skin-versus gut-skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+CD25+ suppressor T cells. Eur J Immunol. 2003 Jun;33(6):1488-96. doi: 10.1002/eji.200323658.
PubMed 12778466Li L, Boussiotis VA. Molecular and functional heterogeneity of T regulatory cells. Clin Immunol. 2011 Dec;141(3):244-52. doi: 10.1016/j.clim.2011.08.011. Epub 2011 Aug 30.
PubMed 21945485Hovhannisyan Z, Treatman J, Littman DR, Mayer L. Characterization of interleukin-17-producing regulatory T cells in inflamed intestinal mucosa from patients with inflammatory bowel diseases. Gastroenterology. 2011 Mar;140(3):957-65. doi: 10.1053/j.gastro.2010.12.002. Epub 2010 Dec 11.
PubMed 21147109Menning A, Loddenkemper C, Westendorf AM, Szilagyi B, Buer J, Siewert C, Hamann A, Huehn J. Retinoic acid-induced gut tropism improves the protective capacity of Treg in acute but not in chronic gut inflammation. Eur J Immunol. 2010 Sep;40(9):2539-48. doi: 10.1002/eji.200939938.
PubMed 20690178Abramson O, Qiu S, Erle DJ. Preferential production of interferon-gamma by CD4+ T cells expressing the homing receptor integrin alpha4/beta7. Immunology. 2001 Jun;103(2):155-63. doi: 10.1046/j.0019-2805.2001.01234.x.
PubMed 11412302El Azreq MA, Boisvert M, Cesaro A, Page N, Loubaki L, Allaeys I, Chakir J, Poubelle PE, Tessier PA, Aoudjit F. alpha2beta1 integrin regulates Th17 cell activity and its neutralization decreases the severity of collagen-induced arthritis. J Immunol. 2013 Dec 15;191(12):5941-50. doi: 10.4049/jimmunol.1301940. Epub 2013 Nov 15.
PubMed 24244022Baaten BJ, Cooper AM, Swain SL, Bradley LM. Location, location, location: the impact of migratory heterogeneity on T cell function. Front Immunol. 2013 Oct 8;4:311. doi: 10.3389/fimmu.2013.00311.
PubMed 24115949Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, Pittet JF, Kaminski N, Garat C, Matthay MA, Rifkin DB, Sheppard D. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 1999 Feb 5;96(3):319-28. doi: 10.1016/s0092-8674(00)80545-0.
PubMed 10025398Travis MA, Reizis B, Melton AC, Masteller E, Tang Q, Proctor JM, Wang Y, Bernstein X, Huang X, Reichardt LF, Bluestone JA, Sheppard D. Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature. 2007 Sep 20;449(7160):361-5. doi: 10.1038/nature06110. Epub 2007 Aug 12.
PubMed 17694047Bridges LC, Sheppard D, Bowditch RD. ADAM disintegrin-like domain recognition by the lymphocyte integrins alpha4beta1 and alpha4beta7. Biochem J. 2005 Apr 1;387(Pt 1):101-8. doi: 10.1042/BJ20041444.
PubMed 15504110
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of CD4+ T Cell Subsets in the Mechanism of Action of Vedolizumab in Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT02721719
- Acronym / sponsor ID
- H15-01034
- Conditions
- Ulcerative Colitis
- Keywords
- Ulcerative Colitis, UC, Vedolizumab, Entyvio, Inflammatory Bowl Disease, IBD, T-Lymphocytes, Regulatory
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- May 2016
- Primary completion
- Dec 2023 (actual)
- Study completion
- Dec 2024 (estimated)
- First posted
- 29 Mar 2016 (estimated)
- 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 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.
Detailed description
Inflammatory bowel disease (IBD) is an umbrella term for Crohn's disease and Ulcerative Colitis (UC), which are thought to be caused by disruption of the intestinal epithelial cell barrier, leading to changes in the intestinal flora and a consequent aberrant activation of the mucosal immune system. The resulting chronic intestinal inflammation is highly dependent on different subsets of CD4+ T helper (Th) cells. For example, correlative data suggest that Crohn's disease is driven by exaggerated Th1 and Th17 cell responses, since inflamed lesions contain increased levels of cytokines associated with these cells including IFNγ, IL-12, and IL-17 and IL-18. In contrast, although Ulcerative Colitis is in the same family of diseases, it is typically associated with Th2 cells since patients have high levels of IL-13 in the intestinal mucosa compared to patients with Crohn's disease or healthy individuals. Recent evidence implicates the newly emerging Th9 subset of Th cells in the pathology of UC. The development and function of Th cells with pathogenic potential is kept in check by another subset of CD4+ T cells, which is known as the regulatory T cell, or Treg. In healthy individuals, the intestinal lamina propria has a large proportion of Tregs, and evidence that simply lacking Tregs leads to IBD, suggests Tregs have a critical role in controlling intestinal homeostasis. Indeed, work in animal models and early phase clinical trials have shown that restoration of Treg function can ameliorate IBD. These data suggest that effective therapies need to promote the function of Tregs. Hence in order to understand the mechanism of action of new therapeutics it is critical to assess their impact on the balance between effector and regulatory CD4+ T cells.
Homing of effector and regulatory T cells to the intestine is controlled by a variety of integrins and chemokine receptors, with evidence that expression of alpha4beta7-integrin molecules (α4β7) on T cells has a key role in this process. Since Vedolizumab (Entyvio) specifically blocks the interaction between α4β7 and its ligands, which are expressed in mucosal tissue, its therapeutic effects in IBD are presumed to be related to a reduction in T cell trafficking to the intestine. However, how this biologic agent specifically affects the homing of Tregs versus effector T cells is unknown. In humans, Tregs in the peripheral blood are reported to express lower levels of α4β7 compared to effector T cells, but the relative expression on different subsets (i.e. Th1, vs. Th2, vs. Th17) of CD4+ T cells is unknown. Interestingly, in the intestine there is also a subset of Tregs that produces IL-17 and expresses high levels of α4β7, but the functional relevance of these cells in IBD is unknown. In addition, in mice, expression of α4β7 on CD4+ T cells is unstable under inflammatory conditions, suggesting that studies with circulating T cells in healthy individuals may not accurately reflect integrin expression in states of inflammation. Understanding how Vedolizumab affects the localization of circulating versus tissue-localized subsets of CD4+ T cells is key to understanding how this therapy works.
Also unknown is how signaling by α4β7 affects the development and/or function of different subsets of CD4+ T cells. In T cells, integrins not only mediate homing, but they also provide tissue-specific signals. For example, they can act as costimulatory molecules 10-12 and influence cytokine production. The molecular basis for the effects on T cells has not been well characterized, but in other cells integrins activate the PI3K pathway, providing a pro-survival signal 16. Since we have shown that activation of the PI3K pathway regulates the balance of effector versus regulatory T cells 17, it is possible that blockade of α4β7 may reduce PI3K signaling and favor the development of Tregs. In support of this possibility, we have shown that fibronectin, which is a ligand for α4β7, inhibits the development of Tregs.
This is an observational study to determine the expression pattern and function of α4β7 on effector and regulatory CD4+ T cells, and to define how treatment with Vedolizumab affects the homing and function of these cells. We hypothesize that that treatment with Vedolizumab will shift the balance of effector and regulatory T cells through two mechanisms: 1) altered migration of different subsets of CD4+ T cells to the intestine; and 2) promoting Treg stability as a consequence of reduced PI3K signaling downstream of α4β7.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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). |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
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
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
2 secondary outcomes
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
- Background: PubMed 21295492Hardenberg G, Steiner TS, Levings MK. Environmental influences on T regulatory cells in inflammatory bowel disease. Semin Immunol. 2011 Apr;23(2):130-8. doi: 10.1016/j.smim.2011.01.012. Epub 2011 Feb 3.
- Background: PubMed 20939860Mallone R, Mannering SI, Brooks-Worrell BM, Durinovic-Bello I, Cilio CM, Wong FS, Schloot NC; T-Cell Workshop Committee, Immunology of Diabetes Society. Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society. Clin Exp Immunol. 2011 Jan;163(1):33-49. doi: 10.1111/j.1365-2249.2010.04272.x. Epub 2010 Oct 5.
- Background: PubMed 24957265Nalleweg N, Chiriac MT, Podstawa E, Lehmann C, Rau TT, Atreya R, Krauss E, Hundorfean G, Fichtner-Feigl S, Hartmann A, Becker C, Mudter J. IL-9 and its receptor are predominantly involved in the pathogenesis of UC. Gut. 2015 May;64(5):743-55. doi: 10.1136/gutjnl-2013-305947. Epub 2014 Jun 23.
- Background: PubMed 11698225Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001 Nov;22(11):633-40. doi: 10.1016/s1471-4906(01)02060-9.
- Background: PubMed 19509315Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER. The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9.
- Background: PubMed 12778466Iellem A, Colantonio L, D'Ambrosio D. Skin-versus gut-skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+CD25+ suppressor T cells. Eur J Immunol. 2003 Jun;33(6):1488-96. doi: 10.1002/eji.200323658.
- Background: PubMed 21945485Li L, Boussiotis VA. Molecular and functional heterogeneity of T regulatory cells. Clin Immunol. 2011 Dec;141(3):244-52. doi: 10.1016/j.clim.2011.08.011. Epub 2011 Aug 30.
- Background: PubMed 21147109Hovhannisyan Z, Treatman J, Littman DR, Mayer L. Characterization of interleukin-17-producing regulatory T cells in inflamed intestinal mucosa from patients with inflammatory bowel diseases. Gastroenterology. 2011 Mar;140(3):957-65. doi: 10.1053/j.gastro.2010.12.002. Epub 2010 Dec 11.
- Background: PubMed 20690178Menning A, Loddenkemper C, Westendorf AM, Szilagyi B, Buer J, Siewert C, Hamann A, Huehn J. Retinoic acid-induced gut tropism improves the protective capacity of Treg in acute but not in chronic gut inflammation. Eur J Immunol. 2010 Sep;40(9):2539-48. doi: 10.1002/eji.200939938.
- Background: PubMed 11412302Abramson O, Qiu S, Erle DJ. Preferential production of interferon-gamma by CD4+ T cells expressing the homing receptor integrin alpha4/beta7. Immunology. 2001 Jun;103(2):155-63. doi: 10.1046/j.0019-2805.2001.01234.x.
- Background: PubMed 24244022El Azreq MA, Boisvert M, Cesaro A, Page N, Loubaki L, Allaeys I, Chakir J, Poubelle PE, Tessier PA, Aoudjit F. alpha2beta1 integrin regulates Th17 cell activity and its neutralization decreases the severity of collagen-induced arthritis. J Immunol. 2013 Dec 15;191(12):5941-50. doi: 10.4049/jimmunol.1301940. Epub 2013 Nov 15.
- Background: PubMed 24115949Baaten BJ, Cooper AM, Swain SL, Bradley LM. Location, location, location: the impact of migratory heterogeneity on T cell function. Front Immunol. 2013 Oct 8;4:311. doi: 10.3389/fimmu.2013.00311.
- Individual participant dataSharing planned: No
Related trials for Ulcerative Colitis
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
RecruitingObservational study
Ibd CAncer and seRious Infections in France (I-CARE 2)
IBD, Ulcerative Colitis
RecruitingObservational study
Characterization of Colorectal Dysplasic Lesions and Stratification of Their Evolving Risk in Inflammatory Bowel Disease Patients: a Prospective, Observational and Multicenter Study
Crohn Disease (CD), Colitis Ulcerative
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease
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.
Brian Bressler, MD, FCRP(C) principal investigator
University of British Columbia
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 Ulcerative Colitis, run by University of British Columbia at 1 site in Canada.
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 3 inclusion and 5 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 17 May 2024. 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 Canada. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). 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 NCT02721719, which also lists 31 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 17 May 2024.