Clinical trial NCT03802214: Ulcerative Colitis - Vedolizumab- With/Without Prior Exposure to Anti-TNF（Tumor Necrosis Factor）Therapy
Official title: A Case-control Study to Evaluate the Immunoinflammatory Effect of Prior Exposure to Anti-TNF Therapy in Patients With Ulcerative Colitis Starting Vedolizumab Therapy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Ulcerative Colitis
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Takeda
name: University of Western Ontario, Canada
name: University of California, San Diego
First posted: 2019-01-14
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: clinical indication for biologic therapy, adult patients (\>18) with the diagnosis of inflammatory bowel disease (Ulcerative Colitis) who are naive or failed anti-TNF therapy previously.

Brief summary: A case-control study to evaluate the immunoinflammatory effect of prior exposure to anti-TNF therapy in patients with ulcerative colitis starting vedolizumab therapy

Detailed description: Inflammatory bowel disease (IBD)- ulcerative colitis (UC) and Crohn's disease (CD)- are chronic conditions of the gastrointestinal tract. Treatment generally consists of immunosuppression to modify the dysregulated immune responses. Vedolizumab, an inhibitor of α4β7, is a highly effective therapy for treating IBD, that minimized adverse effects through its gut selective inhibition of lymphocyte trafficking. However, the mechanism of action remains incompletely characterized especially in those previously treated to other biologics and why some patients are either vedolizumab non-responders or fail to respond over time. We would like to address the question whether anti-TNF non-responders as well as those that either do not respond or fail overtime to respond to vedolizumab identifies a specific population with difficult to treat disease that have alternate trafficking patterns and whether prior exposure to anti-TNF alters the mucosal immune responses, and/or trafficking patterns when compared to anti-TNF naive patients that may help explain impaired response to vedolizumab induction therapy.

Eligibility criteria: Inclusion Criteria:

* adult patients (\>18 years old)
* clinical diagnosis of inflammatory bowel disease (Ulcerative Colitis)
* clinical indication for biologic therapy
* naive or failed anti-TNF therapy previously

Exclusion Criteria:

* patients allergic or intolerant to vedolizumab,
* past use of vedolizumab;
* patient unable to give consent to enter the study

Primary outcomes:
measure: Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells)
timeFrame: changes from enrollment to end of treatment (week 14)
Secondary outcomes:
measure: Analysis of the serum and tissue concentrations of inflammatory markers (interleukins)
timeFrame: changes from enrollment to end of treatment (week 14)
measure: Analysis of the serum and tissue concentrations of vedolizumab
timeFrame: changes from enrollment to end of treatment (week 14)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: London
country: Canada
facility: University of Western Ontario
state: Ontario
Study officials:
affiliation: Stanford University
name: Aida Habtezion, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22;369(8):711-21. doi: 10.1056/NEJMoa1215739.
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