Effects of Gallopamil in Severe Asthma (REMODEL'ASTHME)

University Hospital of Bordeaux

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Placebo.; Drug: Methoxyverapamil (gallopamil)

Study type: Interventional

Funder types: Other

Identifiers

NCT00896428

CHUBX2008/09

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female aged more than 18 years
• Written informed consent
• Diagnosis of severe asthma according to ATS criteria

Exclusion criteria

• Smoker or former smoker
• Chronic viral infections (hepatitis, HIV)
• Aspergillosis
• Pregnancy
• Breastfeeding
• Contraindications to gallopamil or bronchoscopy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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31 participants in 2 patient groups, including a placebo group

1

Experimental group

Description:

16 patients with a diagnosis of severe asthma under gallopamil treatment

Treatment:

Drug: Methoxyverapamil (gallopamil)

2

Placebo Comparator group

Description:

16 patients with a diagnosis of severe asthma under placebo treatment

Treatment:

Drug: Placebo.