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

NCT02712866 | Completed

• 1 other identifier: FIM-VED-2016-01
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Surface and Th17 phenotype markers in T lymphocytes as response predictors

  From drug administration until 14 weeks.

Secondary Outcomes (1)

• Surface and Th17 phenotype markers in T lymphocytes as sustained remission predictors

  From drug administration (week 14th) until 12 months.

Study Arms (1)

Patients treated with vedolizumab

Drug: Vedolizumab

Interventions

Vedolizumab DRUG

Administration of intravenous Vedolizumab in inflammatory bowel disease patients

Patients treated with vedolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Parc de Salut Mar: lead

Study Sites (1)

Hospital del Mar

Barcelona, 08003, Spain

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: March 18, 2016
• Study Start: January 1, 2017
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: February 28, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)