Off Label Use of Infliximab in Adult Patients With Severe Eosinophilic Esophagitis (IEE)

This study has been completed.
Sponsor:
Information provided by:
Swiss EE Study Group
ClinicalTrials.gov Identifier:
NCT00523354
First received: August 30, 2007
Last updated: April 6, 2009
Last verified: April 2009
  Purpose

Eosinophilic Esophagitis (EE) is a chronic inflammatory disorder of the esophagus with a constantly increasing prevalence. It has been demonstrated that the expression of the cytokine TNF-α is up regulated in EE and that this pro-inflammatory cytokine is highly expressed by the keratinocytes of the esophageal epithelium in patients with active EE. Furthermore, it has been shown that TNF-α is capable to induce eotaxin-3 production in keratinocytes. These results suggest that TNF-α plays a crucial role in the pathogenesis of EE. Based on these findings, the investigators plan a prospective T1 translational study with the purpose to evaluate the efficacy of an Infliximab monotherapy in adult patients with severe, corticosteroid-dependent EE.


Condition Intervention Phase
Esophagitis
Drug: Infliximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Proof-of-Concept Study to Analyze the Efficacy of in TNF-Alpha Blockade in Adult Patients With Severe, Corticosteroid-Dependent Eosinophilic Esophagitis

Resource links provided by NLM:


Further study details as provided by Swiss EE Study Group:

Primary Outcome Measures:
  • Tissue eosinophilia before and after therapy

Study Start Date: August 2007
Study Completion Date: October 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 (open-label)
prospective, open label, uncontrolled trial
Drug: Infliximab
Induction therapy with 2 infusions, each 5 mg/kg body weight within 2 wks
Other Name: Remicade

Detailed Description:

Study Principle: An open-conducted, un-controlled, off label use of Infliximab will be performed in at least 3 individuals with Eosinophilic Esophagitis (EE) to evaluate the efficacy of an TNF-α blockade in the treatment of adult patients with severe, isolated EE.

Rationale for this Trial: Eosinophilic Esophagitis is a chronic, TH2-type dominant inflammatory disorder of the esophagus with a constantly increasing prevalence. It has been demonstrated that the cytokines TNF-α and IL-5 as well as the chemokine eotaxin-3 play a crucial role in the immuno-pathogenesis of this disease. These mediators are potential targets for therapeutic interventions. The established diagnostic criteria of EE are PPI-resistent esophageal related symptoms in combination with an infiltration of the esophageal mucosa with more than 20 eosinophils/hpf, a tissue where eosinophils are not normally encountered.

Treatment strategies in chronic inflammations have basically two goals: 1) Relief of symptoms; and 2) Prevention of long-term damage of the affected organ, due to a persistence of an uncontrolled inflammation. Standard recommendations for medical therapy of EE include systemic or topical corticosteroids and leukotriene antagonists. The treatment with corticosteroids is limited by the occurence of steroid-dependence and steroid-resistance, as well as the corticosteroid adherent side effects.

Infliximab, a chimeric monoclonal IgG antibody, is a potent inhibitor of the soluble and the membrane-bound form of TNF-α. Its efficacy in inducing and maintaining a remission in several TH1- and TH2-type inflammations is well documented. Infliximab is since more than 5 years approved for the therapy of these immune-mediated inflammations. Today, it is used as standard therapy in a subset of severe forms in these disorders. Meanwhile an overwhelming mass of data has confirmed the efficacy and the safety of this compound.

Purpose of this Study:The purpose of this pilot-trial is to evaluate the efficacy of a TNF-α blockade with Infliximab monotherapy as induction-treatment in adult patients with severe EE.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients with severe, corticosteroid-dependent eosinophilic esophagitis

Exclusion Criteria:

  • Pregnancy
  • Evidence of latent or active tuberculosis
  • Other contra-indications for TNF-alpha blockers
  • Unstable medical conditions
  • Malignancies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00523354

Locations
Switzerland
EE-Clinics, Praxis Roemerhof
Olten, SO, Switzerland, 4600
Sponsors and Collaborators
Swiss EE Study Group
Investigators
Study Chair: Hans-Uwe Simon, MD and PhD Deaprtment of Pharmacology, University Bern, Bern, Switzerland
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00523354     History of Changes
Other Study ID Numbers: Swiss EE-Study Group
Study First Received: August 30, 2007
Last Updated: April 6, 2009
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss EE Study Group:
Eosinophilic Esophagitis
TNF-alpha
TNF-alpha Blockade
Infliximab

Additional relevant MeSH terms:
Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Infliximab
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents
Antirheumatic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 24, 2014