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

NCT ID: NCT02712866

Last Updated: 2019-02-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 24 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-02-28

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.

Conditions

Inflammatory Bowel Disease

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients treated with vedolizumab

Vedolizumab

Intervention Type: DRUG

Administration of intravenous Vedolizumab in inflammatory bowel disease patients

Interventions

Vedolizumab

Administration of intravenous Vedolizumab in inflammatory bowel disease patients

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parc de Salut Mar

OTHER

Sponsor Role: lead

Responsible Party

Lucia Marquez

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hospital del Mar

Barcelona, , Spain

Countries

Spain

Other Identifiers

FIM-VED-2016-01

Identifier Type: -

Identifier Source: org_study_id