Ulcerative ColitisNCT03802214
Ulcerative Colitis - Vedolizumab- With/Without Prior Exposure to Anti-TNF（Tumor Necrosis Factor）Therapy
An observational study of Ulcerative Colitis, run by Stanford University at 2 sites in 2 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Vedolizumab
- Type of treatment
- Injection or infusion
- How many people
- 1 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 29 Oct 2020to 11 Dec 2020
- 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
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- patients allergic or intolerant to vedolizumab,
- past use of vedolizumab;
- patient unable to give consent to enter the study
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
A case-control study to evaluate the immunoinflammatory effect of prior exposure to anti-TNF therapy in patients with ulcerative colitis starting vedolizumab therapy
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- Vedolizumab
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VedolizumabDrug
Also called Entyvio
standard vedolizumab induction (300mg IV at week 0, 2, 6)
| Study group | Role | What they receive |
|---|---|---|
| vedolizumab-UC-naïve to TNF-antagonist | standard vedolizumab induction therapy for ulcerative colitis patients who are naïve to TNF-antagonist therapy Receives: Drug: Vedolizumab | |
| vedolizumab-UC- previous TNF-antagonist | standard vedolizumab induction therapy for ulcerative colitis patients with previous TNF-antagonist exposure Receives: Drug: Vedolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells)
Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells) in patients with and without prior anti-TNF exposure
Measured: changes from enrollment to end of treatment (week 14)
Secondary outcomes (2)
Analysis of the serum and tissue concentrations of inflammatory markers (interleukins)
Analysis of the serum and tissue concentrations of inflammatory markers (interleukins) in vedolizumab responders versus non-responders
Measured: changes from enrollment to end of treatment (week 14)
Analysis of the serum and tissue concentrations of vedolizumab
Analysis of the serum and tissue concentrations of vedolizumab in patients with and without prior anti-TNF exposure
Measured: changes from enrollment to end of treatment (week 14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2019
- Study start29 Oct 2020
- Primary completion11 Dec 2020
- Study completion11 Dec 2020
Why it stopped: Funding discontinued
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)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 Stanford UniversityThe 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda, University of Western Ontario, Canada, University of California, San Diego
- Responsible party
- Principal investigator, Aida Habtezion, Stanford University
- Investigators
- Aida Habtezion, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03802214
- Sponsor's protocol ID
- IRB48889
- Status last verified
- Dec 2020
- First submitted
- 10 Dec 2018
- Last updated
- 21 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We will share the data through the publication of results. Individual participant data was not promised to be shared.
Publications
Schmitt H, Billmeier U, Dieterich W, Rath T, Sonnewald S, Reid S, Hirschmann S, Hildner K, Waldner MJ, Mudter J, Hartmann A, Grutzmann R, Neufert C, Munster T, Neurath MF, Atreya R. Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn's disease. Gut. 2019 May;68(5):814-828. doi: 10.1136/gutjnl-2017-315671. Epub 2018 May 30.
PubMed 29848778Boden EK, Shows DM, Chiorean MV, Lord JD. Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease. Dig Dis Sci. 2018 Sep;63(9):2419-2429. doi: 10.1007/s10620-018-4924-8. Epub 2018 Jan 25.
PubMed 29372476Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, Ohtani H, Fukuda M, Nakayama J. Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis. Am J Gastroenterol. 2007 Jul;102(7):1499-509. doi: 10.1111/j.1572-0241.2007.01189.x. Epub 2007 Apr 24.
PubMed 17459027Kobayashi M, Hoshino H, Masumoto J, Fukushima M, Suzawa K, Kageyama S, Suzuki M, Ohtani H, Fukuda M, Nakayama J. GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitis. Inflamm Bowel Dis. 2009 May;15(5):697-706. doi: 10.1002/ibd.20827.
PubMed 19067429Sandborn 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.
PubMed 23964933Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.
PubMed 23964932Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, Sandborn WJ, Feagan BG, Reinisch W, Fox I. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 2015 Jul;42(2):188-202. doi: 10.1111/apt.13243. Epub 2015 May 20.
PubMed 25996351
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03802214
- Acronym / sponsor ID
- IRB48889
- Conditions
- Ulcerative Colitis
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Funding discontinued
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Takeda, University of Western Ontario, Canada, University of California, San Diego
- Study start
- 29 Oct 2020 (actual)
- Primary completion
- 11 Dec 2020 (actual)
- Study completion
- 11 Dec 2020 (actual)
- First posted
- 14 Jan 2019 (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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| vedolizumab-UC-naïve to TNF-antagonist | – | Drug: Vedolizumabstandard vedolizumab induction therapy for ulcerative colitis patients who are naïve to TNF-antagonist therapy |
| vedolizumab-UC- previous TNF-antagonist | – | Drug: Vedolizumabstandard vedolizumab induction therapy for ulcerative colitis patients with previous TNF-antagonist exposure |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- patients allergic or intolerant to vedolizumab,
- past use of vedolizumab;
- patient unable to give consent to enter the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VedolizumabAlso: Entyviostandard vedolizumab induction (300mg IV at week 0, 2, 6) | Drug | vedolizumab-UC- previous TNF-antagonist, vedolizumab-UC-naïve to TNF-antagonist |
Primary outcome
Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells)
Time frame: changes from enrollment to end of treatment (week 14)
Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells) in patients with and without prior anti-TNF exposure
2 secondary outcomes
Analysis of the serum and tissue concentrations of inflammatory markers (interleukins)
Time frame: changes from enrollment to end of treatment (week 14)
Analysis of the serum and tissue concentrations of vedolizumab
Time frame: changes from enrollment to end of treatment (week 14)
Results and safety
The study was stopped early (reason given: Funding discontinued). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2020.
- Background: PubMed 29848778Schmitt H, Billmeier U, Dieterich W, Rath T, Sonnewald S, Reid S, Hirschmann S, Hildner K, Waldner MJ, Mudter J, Hartmann A, Grutzmann R, Neufert C, Munster T, Neurath MF, Atreya R. Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn's disease. Gut. 2019 May;68(5):814-828. doi: 10.1136/gutjnl-2017-315671. Epub 2018 May 30.
- Background: PubMed 29372476Boden EK, Shows DM, Chiorean MV, Lord JD. Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease. Dig Dis Sci. 2018 Sep;63(9):2419-2429. doi: 10.1007/s10620-018-4924-8. Epub 2018 Jan 25.
- Background: PubMed 17459027Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, Ohtani H, Fukuda M, Nakayama J. Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis. Am J Gastroenterol. 2007 Jul;102(7):1499-509. doi: 10.1111/j.1572-0241.2007.01189.x. Epub 2007 Apr 24.
- Background: PubMed 19067429Kobayashi M, Hoshino H, Masumoto J, Fukushima M, Suzawa K, Kageyama S, Suzuki M, Ohtani H, Fukuda M, Nakayama J. GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitis. Inflamm Bowel Dis. 2009 May;15(5):697-706. doi: 10.1002/ibd.20827.
- Background: PubMed 23964933Sandborn 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.
- Background: PubMed 23964932Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.
- Background: PubMed 25996351Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, Sandborn WJ, Feagan BG, Reinisch W, Fox I. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 2015 Jul;42(2):188-202. doi: 10.1111/apt.13243. Epub 2015 May 20.
- Individual participant dataSharing planned: No. We will share the data through the publication of results. Individual participant data was not promised to be shared.
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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.
Aida Habtezion, MD principal investigator
Stanford University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ulcerative Colitis, run by Stanford University at 2 sites in 2 countries.
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 4 inclusion and 3 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: stopped early, as of the sponsor's last update on 21 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, 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?
The study was stopped early (reason given: Funding discontinued). 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?
Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells) (time frame: changes from enrollment to end of treatment (week 14)). 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 NCT03802214, which also lists 7 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 21 Dec 2020.