Targeting Oxidative Stress in Chronic Beryllium Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Jewish Health
Sponsor:
Information provided by (Responsible Party):
Lisa Maier, National Jewish Health
ClinicalTrials.gov Identifier:
NCT01088243
First received: March 15, 2010
Last updated: February 3, 2014
Last verified: February 2014

March 15, 2010
February 3, 2014
March 2010
June 2014   (final data collection date for primary outcome measure)
Beryllium lymphocyte proliferation responses (BeLPT) [ Time Frame: baseline and week 6 ] [ Designated as safety issue: No ]
Primary endpoints are beryllium proliferation responses (BeLPT) in PBMCs and BAL cells.
Same as current
Complete list of historical versions of study NCT01088243 on ClinicalTrials.gov Archive Site
  • Th1 cytokines [ Time Frame: baseline and week 6 ] [ Designated as safety issue: No ]
    Secondary outcomes include changes in Th1 cytokines (e.g. INFγ)
  • Steady-state GSH levels [ Time Frame: baseline and week 6 ] [ Designated as safety issue: No ]
    Secondary outcomes include changes in steady-state GSH levels in beryllium specific CD4+ T cell, HDAC2 levels
  • HDAC2 levels [ Time Frame: baseline and week 6 ] [ Designated as safety issue: No ]
    Secondary outcomes include changes in HDAC2 levels
  • Glucocorticoid receptors [ Time Frame: baseline and week 6 ] [ Designated as safety issue: No ]
    Secondary outcomes include changes in glucocorticoid receptors modification in PBMCs and BAL cells.
  • Lung function [ Time Frame: baseline and week 6 ] [ Designated as safety issue: No ]
    Secondary outcomes include changes in lung function, which will be assessed with spirometry and DLCO.
Same as current
Not Provided
Not Provided
 
Targeting Oxidative Stress in Chronic Beryllium Disease
Targeting Oxidative Stress in Chronic Beryllium Disease

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Chronic Beryllium Disease
  • Drug: Mesalamine
    Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
    Other Names:
    • Pentasa
    • 5-ASA
    • Mesalamine
  • Drug: Placebo
    Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
  • Experimental: Mesalamine
    Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
    Intervention: Drug: Mesalamine
  • Placebo Comparator: Placebo
    Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
June 2014
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of chronic beryllium disease based on the criteria below:

    1. History of beryllium exposure, and;
    2. Positive blood and/or bronchoalveolar lavage Beryllium Lymphocyte Proliferation Tests (BeLPT), and;
    3. Biopsy-proven pathologic changes consistent with CBD-non-caseating granulomas and/or mononuclear cell interstitial infiltrates, and;
    4. Positive bronchoalveolar lavage (BAL) BeLPT and > 15% lymphocytes in BAL fluid.

Exclusion Criteria:

  • History of Hepatic disease
  • History of Renal disease
  • Hypersensitivity to Pentasa (5-ASA) or salicylates.
  • Pregnancy
  • Presence of another disease that may be expected to significantly affect patient mortality (e.g., HIV), severe cor pulmonale);
  • The use of blood thinners.
  • Current use of tobacco (smoking or otherwise) in the past 6 months
  • Patient inability to participate in the study, such as inability to undergo venipuncture and BAL procedures (if undergoing bronchoscopy) that form part of the inclusion/exclusion criteria or part of the outcome measure.

If undergoing bronchoscopy:

  • Severe room air hypoxemia (precluding transbronchial lung biopsy and/or BAL), e.g., pO2 < 45 (Denver altitude 5,280 feet);
Both
18 Years to 80 Years
No
Contact: Briana Q Barkes, MPH (303)398-1699 BarkesB@NJHealth.org
United States
 
NCT01088243
HS-2360B
Yes
Lisa Maier, National Jewish Health
National Jewish Health
Not Provided
Principal Investigator: Lisa A. Maier, M.D., MSPH National Jewish Health
Principal Investigator: Brian Day, PhD National Jewish Health
National Jewish Health
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP