Targeting Oxidative Stress in Chronic Beryllium Disease
Condition: Chronic Beryllium Disease
MeSH terms: Berylliosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to understand if a drug called mesalamine helps to control
      inflammation associated with chronic beryllium disease (CBD). We hypothesize that in CBD
      subjects treated with prednisone, mesalamine treatment will enhance the immunosuppressive
      effects of prednisone, and thus reduce the immune response to beryllium.
    

Detailed description: 
      The overall goal of this study is to understand the role of oxidative stress as a potential
      therapeutic target in the pathogenesis of chronic beryllium disease (CBD). CBD is an
      inflammatory hypersensitivity lung disease that occurs in an estimated 800,000
      beryllium-exposed workers in the United Sates. CBD is characterized by the presence of
      pulmonary non-caseating granulomas with accumulation of macrophages and beryllium specific
      CD4+ T cells (Newman et al. 1998). Upon beryllium stimulation in vitro, beryllium specific
      CD4+ T cells proliferate and produce Th1 cytokines (i.e. TNF-α, IFN-γ, and IL-2) at unusually
      high levels (Tinkle et al. 1997). The molecular mechanism(s) by which beryllium regulates the
      chronic production of these cytokines is unknown. Exciting preliminary studies indicate that
      beryllium alters the redox status of T cells which may adversely modulate the immune response
      in CBD. Based on these points, a novel hypothesis is proposed: 1) oxidative stress enhances
      the T cells response to antigen and this enhancement may explain both the excessive cytokine
      response and the pathogenesis of pulmonary granulomas in CBD and; 2) an inherent difference
      in T cell antioxidant status is a critical factor in the pathogenesis of CBD. This proposal
      is a pilot clinical trial examining an approved drug for the treatment of ulcerative colitis
      (5-amino salicylic acid, 5-ASA), which has anti-inflammatory and antioxidant properties, as a
      potential new approach for CBD treatment. In this clinical trial, 40 CBD subjects already
      treated with prednisone, will be treated with either placebo or 5-ASA to determine it effects
      on the beryllium stimulated immune response in the lung by undergoing bronchoscopy with
      bronchoalveolar lavage and in blood by undergoing venipuncture before and after 6 weeks of
      treatment with 5-ASA. As a secondary outcome, we will also assess subjects clinical response
      to this short course of 5-ASA using spirometry. Bronchoscopies are optional. Patients have
      the option to participate by undergoing venipuncture and lung function tests only.
    

Intervention name(s): Mesalamine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.; Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Other intervention name(s): Pentasa; 5-ASA; Sugar Pill
Intervention MeSH terms: Mesalamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Berylliosis; Beryllium Disease