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Effects of Gallopamil in Severe Asthma (REMODEL'ASTHME)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00896428
Recruitment Status : Completed
First Posted : May 11, 2009
Last Update Posted : August 14, 2013
Information provided by (Responsible Party):
University Hospital, Bordeaux

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.

Condition or disease Intervention/treatment Phase
Asthma Drug: Methoxyverapamil (gallopamil) Drug: Placebo. Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Gallopamil on Bronchial Smooth Muscle Remodelling in Severe Asthma: a Double Blind Study.
Study Start Date : December 2009
Actual Primary Completion Date : July 2012
Actual Study Completion Date : November 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: 1
16 patients with a diagnosis of severe asthma under gallopamil treatment
Drug: Methoxyverapamil (gallopamil)
200 mg/day (1 tablet 100 mg morning and evening) for 12 months.

Placebo Comparator: 2
16 patients with a diagnosis of severe asthma under placebo treatment
Drug: Placebo.
1 tablet morning and evening for 12 months

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

Secondary Outcome Measures :
  1. Bronchial smooth muscle remodelling assessed by electron microscopy [ Time Frame: Before and after 12 months treatment. ]
  2. Bronchial smooth muscle mitochondrial number and activity assessed in vitro [ Time Frame: Before and after 12 months treatment. ]
  3. Bronchial thickness assessed by 3D analysis of computed tomography [ Time Frame: Before and after 12 months treatment. ]
  4. 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. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00896428

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Hôpital Haut-Lévêque - Centre Hospitalier Universitaire de Bordeaux
Pessac, France, 33604
Sponsors and Collaborators
University Hospital, Bordeaux
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Principal Investigator: Patrick Berger, Professor University Hospital Bordeaux, France

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University Hospital, Bordeaux Identifier: NCT00896428    
Other Study ID Numbers: CHUBX2008/09
First Posted: May 11, 2009    Key Record Dates
Last Update Posted: August 14, 2013
Last Verified: August 2013
Keywords provided by University Hospital, Bordeaux:
airway remodelling
smooth muscle
Additional relevant MeSH terms:
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Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs