Effects of Gallopamil in Severe Asthma

Asthma Clinical Trial

— REMODEL'ASTHME  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00896428
• Other study ID #: CHUBX2008/09
• Status: Completed
• Phase: Phase 2
• First received: May 7, 2009
• Last updated: August 13, 2013
• Start date: December 2009
• Est. completion date: November 2012

Study information

• Verified date: August 2013
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: November 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Methoxyverapamil (gallopamil)
200 mg/day (1 tablet 100 mg morning and evening) for 12 months.
• Placebo.
1 tablet morning and evening for 12 months

Locations

Country	Name	City	State
France	Hôpital Haut-Lévêque - Centre Hospitalier Universitaire de Bordeaux	Pessac

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

References & Publications (1)

Trian T, Benard G, Begueret H, Rossignol R, Girodet PO, Ghosh D, Ousova O, Vernejoux JM, Marthan R, Tunon-de-Lara JM, Berger P. Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma. J Exp Med. 2007 Dec 24;204(13):3173-81. Epub 2007 Dec 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bronchial smooth muscle remodelling assessed by optic microscopy.		Before and after 12 months treatment.	No
Secondary	Bronchial smooth muscle remodelling assessed by electron microscopy		Before and after 12 months treatment.	No
Secondary	Bronchial smooth muscle mitochondrial number and activity assessed in vitro		Before and after 12 months treatment.	No
Secondary	Bronchial thickness assessed by 3D analysis of computed tomography		Before and after 12 months treatment.	No
Secondary	Asthma control using asthma control questionnaire, inflammation monitoring, number of hospitalizations, number of emergency visits, number of unplanned medical visits.		Once per month for 12 months.	No