a4b7 Integrin in Eosinophilic Esophagitis

Investigating the Role of a4b7 Integrin as a Therapeutic Target in Eosinophilic Esophagitis

The overall objective of this preclinical study is to further the investigators mechanistic understanding of the role that the α4β7 and mucosal addressin cell adhesion molecule (MAdCAM-1) pathway plays in mediating eosinophil recruitment in EoE. To accomplish this, the investigators aim to (1) determine the baseline and dynamic patterns of α4β7 integrin expression on circulating and tissue eosinophils in EoE and in the setting of non-EoE esophageal eosinophilia (e.g., reflux esophagitis) and (2) determine the complete profile of eosinophil integrin molecules that may play a role in active EoE.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis
• Intervention / Treatment: Other: Eosinophil isolation and characterization.

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with active eosinophilic esophagitis

Description

Inclusion Criteria:

1. Able to give written informed consent
2. Male or female patients aged 18-65 years at time of screening
3. Confirmed active EoE at screening or within 8 weeks prior to baseline visit, as defined by esophageal mucosal eosinophils ≥15 per high power field (HPF, 400X magnification) despite at least 4 weeks of proton pump inhibitor (PPI) therapy with omeprazole 20 mg twice daily or the equivalent. updated 14APR2015 Page 8 of 19
4. Within the week prior to dosing, patient has one of the following symptoms of moderate, or worse, severity: dysphagia, vomiting, regurgitation, abdominal pain, chest pain/heartburn.
5. Maintained on a stabilized diet for at least 6 weeks prior to screening and during the course of the study; stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups.
6. Willing and able to comply with all clinic visits and study-related procedures
7. Able to understand and complete study-related questionnaires

Exclusion Criteria:

1. Another disorder that causes esophageal eosinophilia (e.g., hypereosinophilic syndrome, Churg-Strauss, parasitic infection)
2. History of abnormal gastric or duodenal biopsy or documented GI disorders other than EoE (e.g., celiac disease, Crohn's disease or H. pylori infection)
3. History of the following GI surgeries: fundoplication, gastric surgery or surgery for esophageal atresia
4. Use of systemic immunosuppressive or immunomodulating agents (oral prednisone, anti-immunoglobulin E (IgE) monoclonal antibody (mAb), methotrexate, cyclosporine, INFα, or anti-TNF) within six months prior to study entry.
5. A stricture on endoscopy that prevents passage of the endoscope
6. Participation in any investigational drug or device study within 30 days prior to study entry.
7. Female subjects who are pregnant or nursing.
8. Chronic infections such as HIV, hepatitis B or C, active mycobacterial (TB) or fungal infections.
9. Neoplasm or a history of malignancy in the preceding 5 years.
10. Concurrent infection or disease that may preclude assessment of eosinophilic esophagitis.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adults with EoE; Adult patients with active eosinophilic esophagitis will under blood collection and esophagus biopsies in order to perform eosinophil isolation and characterization.	Other: Eosinophil isolation and characterization.; Peripheral blood and esophageal biopsies will be obtained from study subjects for further analysis of eosinophils integrin profiles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of eosinophils expressing a4b7 integrin	Eosinophil expression levels of a4b7 integrin will be assessed on peripheral and esophageal eosinophils during active EoE and after treatment-induced remission.	8 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: John J Garber, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: September 8, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimate): September 10, 2015

Study Record Updates

• Last Update Posted (Actual): February 21, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: EoE; eosinophilic esophagitis; integrins
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis
• Other Study ID Numbers: 2015P000816