Effects of Gallopamil in Severe Asthma (REMODEL'ASTHME)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT00896428
First received: May 7, 2009
Last updated: August 13, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Asthma
Drug: Methoxyverapamil (gallopamil)
Drug: Placebo.
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Gallopamil on Bronchial Smooth Muscle Remodelling in Severe Asthma: a Double Blind Study.

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Bronchial smooth muscle remodelling assessed by optic microscopy. [ Time Frame: Before and after 12 months treatment. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bronchial smooth muscle remodelling assessed by electron microscopy [ Time Frame: Before and after 12 months treatment. ] [ Designated as safety issue: No ]
  • Bronchial smooth muscle mitochondrial number and activity assessed in vitro [ Time Frame: Before and after 12 months treatment. ] [ Designated as safety issue: No ]
  • Bronchial thickness assessed by 3D analysis of computed tomography [ Time Frame: Before and after 12 months treatment. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: December 2009
Study Completion Date: November 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00896428

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

Publications:
Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT00896428     History of Changes
Other Study ID Numbers: CHUBX2008/09
Study First Received: May 7, 2009
Last Updated: August 13, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Asthma
gallopamil
airway remodelling
smooth muscle

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Gallopamil
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014