Effects of Gallopamil in Severe Asthma
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.
Description
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.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Conditions
Asthma
Intervention
Methoxyverapamil (gallopamil), Placebo.
Location
Hôpital Haut-Lévêque - Centre Hospitalier Universitaire de Bordeaux
Pessac
France
33604
Status
Not yet recruiting
Source
University Hospital, Bordeaux
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00896428
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Gallopamil
Coronary vasodilator that is an analog of iproveratril (VERAPAMIL) with one more methoxy group on the benzene ring.
Therapeutic Misconception
Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.
Placebo Effect
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
Asthma, Exercise-induced
Asthma attacks following a period of exercise. Usually the induced attack is short-lived and regresses spontaneously. The magnitude of postexertional airway obstruction is strongly influenced by the environment in which exercise is performed (i.e. inhalation of cold air during physical exertion markedly augments the severity of the airway obstruction; conversely, warm humid air blunts or abolishes it).
Anti-asthmatic Agents
Drugs that are used to treat asthma.
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