Early Biomarkers in Circulating α 4β7 + T Cells to Predict Response to Vedolizumab in Inflamatory Bowel Disease Patients.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02712866
Recruitment Status : Not yet recruiting
First Posted : March 18, 2016
Last Update Posted : June 6, 2016
Information provided by (Responsible Party):
Lucia Marquez, Parc de Salut Mar

Brief Summary:

Background: Infiltration of GI by T lymphocytes is a pathogenic mechanism both in ulcerative colitis (UC) and in Crohn's disease (CD). Vedolizumab (VDZ) is a humanized monoclonal antibody binding with high affinity to α4β7 integrin blocking α4β7+-MAdCAM-1 interaction, hence blocking a key step in GI lymphocytes T infiltration. VDZ has demonstrated a therapeutic effect in UC and CD. Investigators still lack of adequate biomarkers to predict clinical response to biological treatments, specially avoiding invasive procedures.

Objective: Study whether circulating CD4+ and CD8+ α4β7+ memory T lymphocytes and some of their surface markers might be molecular markers of response to VDZ treatment in patients with UC and CD.

Methods: Prospective (pilot) study including 24 adult IBD patients (12 UC patients and 12 CD patients (patients with fistulizing perianal disease will be excluded) with active disease and prior failure to anti-TNFα treatments starting treatment with VDZ. They will received VDZ in standard induction (300mg intravenously, 0-2-6 weeks) and maintenance schemes (300mg intravenously, every 8 weeks).

Epidemiological and clinical data from every patient will be recorded prospectively. Disease activity at weeks 0, 2, 6 and 14 weeks will be evaluated through validated clinical scores, biological parameters and fecal biomarkers.

At week 14 response to the treatment will be evaluated by ileocolonoscopy or enteroMRI.

Peripheral blood will be obtained from every patient at baseline, before the third infusion of VDZ (6th week) and before the first maintenance dose (14th week).

Blood lymphocytes will be isolated and multicolor flow cytometry will be performed on stored circulating memory T cells.

Percentage and absolute values of circulating CD4+ and CD8+ α4β7+ memory T lymphocytes as well as several surface markers related to their activation state (HLA-DR, CD25), Th17 phenotype (IL23R, CCR6, intracellular IL17A) and Th1 phenotype (INFγ)will be assessed on α4β7+ memory T cells.

Condition or disease Intervention/treatment
Inflammatory Bowel Disease Drug: Vedolizumab

Study Type : Observational
Estimated Enrollment : 24 participants
Observational Model: Case-Only
Time Perspective: Prospective
Study Start Date : July 2016
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Vedolizumab
U.S. FDA Resources

Group/Cohort Intervention/treatment
Patients treated with vedolizumab Drug: Vedolizumab
Administration of intravenous Vedolizumab in inflammatory bowel disease patients

Primary Outcome Measures :
  1. Surface and Th17 phenotype markers in T lymphocytes as response predictors [ Time Frame: From drug administration until 14 weeks. ]

Secondary Outcome Measures :
  1. Surface and Th17 phenotype markers in T lymphocytes as sustained remission predictors [ Time Frame: From drug administration (week 14th) until 12 months. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
24 adults with inflammatory bowel disease (12 Ulcerative colitis patients and 12 Chron Disease patients with active disease and prior failure to anti-TNFα treatments (inadequate response, loss of response, intolerance), starting treatment with Vedolizumab.

Inclusion Criteria:

  • Ulcerative colitis or Crohn's disease diagnosis established by Lennard-Jones criteria
  • Clinically active disease confirmed by endoscopic or radiologic criteria Magnetic Resonance Image (MRI)
  • >18 years of age
  • Intolerant, refractory or secondary loss of response to anti-Anti-tumour necrosis factor (TNF) alfa treatment.

Exclusion Criteria:

  • Crohn's disease with perianal disease
  • Active Tuberculosis
  • Current infections (including Clostridium difficile and Cytomegalovirus)
  • History of cancer, including hematologic malignancy and solid tumours within 5 years before
  • History of demyelinating disease
  • Pregnancy or breastfeeding

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 identifier (NCT number): NCT02712866

Contact: Lucía Márquez Mosquera, MD, PhD 0034625910982

Hospital del Mar Not yet recruiting
Barcelona, Spain, 08003
Contact: Lucia Márquez Mosquera, MD, PhD    0034625910982   
Sponsors and Collaborators
Parc de Salut Mar

Responsible Party: Lucia Marquez, MD, PhD, Parc de Salut Mar Identifier: NCT02712866     History of Changes
Other Study ID Numbers: FIM-VED-2016-01
First Posted: March 18, 2016    Key Record Dates
Last Update Posted: June 6, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Intestinal Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Agents