Effects of Gallopamil in Severe Asthma (REMODEL'ASTHME)

August 13, 2013 updated by: University Hospital, Bordeaux

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Pessac, France, 33604
        • Hôpital Haut-Lévêque - Centre Hospitalier Universitaire de Bordeaux

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Bronchial smooth muscle remodelling assessed by optic microscopy.
Time Frame: Before and after 12 months treatment.
Before and after 12 months treatment.

Secondary Outcome Measures

Outcome Measure
Time Frame
Bronchial smooth muscle remodelling assessed by electron microscopy
Time Frame: Before and after 12 months treatment.
Before and after 12 months treatment.
Bronchial smooth muscle mitochondrial number and activity assessed in vitro
Time Frame: Before and after 12 months treatment.
Before and after 12 months treatment.
Bronchial thickness assessed by 3D analysis of computed tomography
Time Frame: Before and after 12 months treatment.
Before and after 12 months treatment.
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.
Once per month for 12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Investigators

  • Principal Investigator: Patrick Berger, Professor, University Hospital Bordeaux, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (ACTUAL)

July 1, 2012

Study Completion (ACTUAL)

November 1, 2012

Study Registration Dates

First Submitted

May 7, 2009

First Submitted That Met QC Criteria

May 8, 2009

First Posted (ESTIMATE)

May 11, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

August 14, 2013

Last Update Submitted That Met QC Criteria

August 13, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX2008/09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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