Clinical Trial: Beryllium Infliximab Study: Clinical Interventional Trial

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Clinical Efficacy of Remicade in Chronic Beryllium Disease: A Randomized, Double-Blind, Placebo-Controlled, Investigator Initiated Trial

Brief Summary: The goal of this research study is to test the clinical effectiveness of a drug called infliximab (Remicade) in chronic beryllium disease (CBD). This drug may reduce tumor necrosis factor-alpha (TNF-a), which is associated with more severe disease and inflammation in the lung. Receiving infliximab may help with symptoms, and may improve clinical testing data normally ordered by your doctor, such as breathing tests. Baseline and follow-up testing will look for improvements in breathing tests (pulmonary function testing), exchange of oxygen in the lungs (exercise test), chest x ray, and lung inflammation.

Detailed Summary:

Hypothesis:

The central hypothesis of this study is that infliximab will prove to be efficacious in the treatment of chronic beryllium disease (CBD), and that it will do so by inhibiting beryllium specific T cell proliferation and cytokine production.

Specific Aims:

Specific Aim 1: To determine the clinical effectiveness of infliximab on chronic beryllium disease. The efficacy of infliximab will be measured by improvement in arterial gas exchange, or arterial alveolar oxygen gradient (A-ad02) at end exercise in subjects with CBD who remain symptomatic and with pulmonary impairment despite current treatment with prednisone and/or methotrexate. Secondary outcome measures will include change in airflow, lung volume, diffusing capacity (DLCO), profusion of small opacities on chest x-ray, dyspnea score, and quality of life questionnaires.

Specific Aim 2: To determine the effect of infliximab on intermediate markers of biological function in CBD. In vitro studies will examine the effect of infliximab on blood and lung cells in culture, as measured by a decrease in beryllium (Be)-stimulated lymphocyte proliferation; a decrease in Be-stimulated cytokine production, including TNF-a, IFN-g, and IL-2; altered Be-stimulated apoptosis of macrophages or lymphocytes.

Research Design and Methods: Since no information is available regarding the pharmacokinetics of infliximab in patients with CBD, the pharmacokinetic information available from the use of infliximab in other similar inflammatory conditions formed the basis for selecting the dose regimen for this protocol. Particularly, a 5mg/kg dose will be used for this study, based on the dose selection used in the sarcoidosis protocol C0168T
Sponsor: Maier, Lisa, M.D.

Current Primary Outcome: A-a Gradient at End Exercise [ Time Frame: after 28 week follow-up. The Alveolar-arterial gradient (A-a gradient), is a measure of the difference between the alveolar partial pressure (A) of oxygen and the arterial (a) partial pressure of oxygen ]

change in end-exercise A-a gradient


Original Primary Outcome: arterial alveolar oxygen gradient (A-adO2) at end exercise between baseline and week 28

Current Secondary Outcome:

Original Secondary Outcome:

  • airflow
  • lung volume
  • diffusing capacity (DLCO)
  • profusion of small opacities on chest x-ray
  • dyspnea score
  • quality of life (QOL) questionnaires


Information By: Maier, Lisa, M.D.

Dates:
Date Received: May 26, 2005
Date Started: February 2005
Date Completion:
Last Updated: May 3, 2016
Last Verified: March 2016