Clinical Trial: Effects of Gallopamil in Severe Asthma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effects of Gallopamil on Bronchial Smooth Muscle Remodelling in Severe Asthma: a Double Blind Study.

Brief Summary: Severe asthma is a difficult to treat disease, characterized by bronchial remodelling, which is an abnormal repair process that contributes to the development of poorly reversible airway narrowing. Such remodelling is now considered as one of the main prognostic factors. Gallopamil-sensitive calcium influx plays a key role in this remodelling process in vitro. The objective of this study is to compare the effects of gallopamil versus placebo on the bronchial smooth muscle remodelling in severe asthmatic patients.

Detailed Summary: Bronchial remodelling mainly involves an increased mass of bronchial smooth muscle (BSM), which is related with an increase proliferation of smooth muscle cells. Recently, using BSM cells obtained from severe asthmatics, we have demonstrated that such an increase proliferation was induced by an activation cascade (Trian, J Exp Med, 2007). It first started with a gallopamil-sensitive calcium influx which induced the activation of calcium-calmodulin kinase IV (CamK-IV). CamK-IV then enhanced mitochondrial biogenesis through the subsequent activation of various transcription factors including PGC-1α, NRF-1 and mt-TFA. BSM cell proliferation was mainly mitochondria-dependent in vitro in severe asthma whereas that of controls was virtually mitochondria-independent. However, in vivo effects of gallopamil remain to be investigated. We will thus enrol 32 severe asthmatic patients in a phase 2 randomized double blind study against placebo and evaluate the effect of gallopamil on BSM remodelling. Since inflammation also activates mitochondrial biogenesis in BSM cells, we will initially optimized asthma treatment for 3 months by both controlling co morbidities and decreasing bronchial inflammation using exhaled NO and eosinophil count within the induced sputum. We will then perform fiberoptic fibroscopy before and after 12 month treatment with gallopamil.
Sponsor: University Hospital, Bordeaux

Current Primary Outcome: Bronchial smooth muscle remodelling assessed by optic microscopy. [ Time Frame: Before and after 12 months treatment. ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Bronchial smooth muscle remodelling assessed by electron microscopy [ Time Frame: Before and after 12 months treatment. ]
  • Bronchial smooth muscle mitochondrial number and activity assessed in vitro [ Time Frame: Before and after 12 months treatment. ]
  • Bronchial thickness assessed by 3D analysis of computed tomography [ Time Frame: Before and after 12 months treatment. ]
  • Asthma control using asthma control questionnaire, inflammation monitoring, number of hospitalizations, number of emergency visits, number of unplanned medical visits. [ Time Frame: Once per month for 12 months. ]


Original Secondary Outcome: Same as current

Information By: University Hospital, Bordeaux

Dates:
Date Received: May 7, 2009
Date Started: December 2009
Date Completion:
Last Updated: August 13, 2013
Last Verified: August 2013