AsthmaPhase 2REMODEL'ASTHMENCT00896428
Effects of Gallopamil in Severe Asthma
A Phase 2 study testing Methoxyverapamil (gallopamil) in people with Asthma, run by University Hospital, Bordeaux at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- Methoxyverapamil (gallopamil)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2009to Nov 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged more than 18 years
- Written informed consent
- Diagnosis of severe asthma according to ATS criteria
Who cannot join
- Smoker or former smoker
- Chronic viral infections (hepatitis, HIV)
- Aspergillosis
- Pregnancy
- Breastfeeding
- Contraindications to gallopamil or bronchoscopy
Trial locations and contacts
1 site in 1 country.
France1 site
Hôpital Haut-Lévêque - Centre Hospitalier Universitaire de Bordeaux
Pessac, 33604
About this study
Official title: 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.
Read the 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.
- Conditions
- Asthma
- Being tested
- Methoxyverapamil (gallopamil), Placebo.
- Keywords
- Asthma, gallopamil, airway remodelling, smooth muscle
- Medical subject headings
- Asthma, Airway Remodeling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methoxyverapamil (gallopamil)Drug
200 mg/day (1 tablet 100 mg morning and evening) for 12 months.
Placebo.Drug
1 tablet morning and evening for 12 months
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 16 patients with a diagnosis of severe asthma under gallopamil treatment Receives: Drug: Methoxyverapamil (gallopamil) |
| 2 | Placebo comparator | 16 patients with a diagnosis of severe asthma under placebo treatment Receives: Drug: Placebo. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bronchial smooth muscle remodelling assessed by optic microscopy.
Measured: Before and after 12 months treatment.
Secondary outcomes (4)
Bronchial smooth muscle remodelling assessed by electron microscopy
Measured: Before and after 12 months treatment.
Bronchial smooth muscle mitochondrial number and activity assessed in vitro
Measured: Before and after 12 months treatment.
Bronchial thickness assessed by 3D analysis of computed tomography
Measured: 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.
Measured: Once per month for 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2009 (estimated)
- Study startDec 2009
- Primary completionJul 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Patrick Berger, Professor, Principal investigator, University Hospital Bordeaux, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00896428
- Sponsor's protocol ID
- CHUBX2008/09
- Acronym
- REMODEL'ASTHME
- Status last verified
- Aug 2013
- First submitted
- 7 May 2009
- Last updated
- 14 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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. doi: 10.1084/jem.20070956. Epub 2007 Dec 3.
PubMed 18056286Girodet PO, Dournes G, Thumerel M, Begueret H, Dos Santos P, Ozier A, Dupin I, Trian T, Montaudon M, Laurent F, Marthan R, Berger P. Calcium channel blocker reduces airway remodeling in severe asthma. A proof-of-concept study. Am J Respir Crit Care Med. 2015 Apr 15;191(8):876-83. doi: 10.1164/rccm.201410-1874OC.
PubMed 25633090
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Gallopamil on Bronchial Smooth Muscle Remodelling in Severe Asthma: a Double Blind Study.
- ClinicalTrials.gov ID
- NCT00896428
- Acronym / sponsor ID
- REMODEL'ASTHME / CHUBX2008/09
- Conditions
- Asthma
- Keywords
- Asthma, gallopamil, airway remodelling, smooth muscle
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 11 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Methoxyverapamil (gallopamil)16 patients with a diagnosis of severe asthma under gallopamil treatment |
| 2 | Placebo comparator | Drug: Placebo.16 patients with a diagnosis of severe asthma under placebo treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female aged more than 18 years
- Written informed consent
- Diagnosis of severe asthma according to ATS criteria
Key exclusion criteria (6 listed)
- Smoker or former smoker
- Chronic viral infections (hepatitis, HIV)
- Aspergillosis
- Pregnancy
- Breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methoxyverapamil (gallopamil)200 mg/day (1 tablet 100 mg morning and evening) for 12 months. | Drug | 1 |
| Placebo.1 tablet morning and evening for 12 months | Drug | 2 |
Primary outcome
Bronchial smooth muscle remodelling assessed by optic microscopy.
Time frame: Before and after 12 months treatment.
4 secondary outcomes
Bronchial smooth muscle remodelling assessed by electron microscopy
Time frame: Before and after 12 months treatment.
Bronchial smooth muscle mitochondrial number and activity assessed in vitro
Time frame: Before and after 12 months treatment.
Bronchial thickness assessed by 3D analysis of computed tomography
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2013.
- Background: PubMed 18056286Trian 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. doi: 10.1084/jem.20070956. Epub 2007 Dec 3.
- Derived from this study: PubMed 25633090Girodet PO, Dournes G, Thumerel M, Begueret H, Dos Santos P, Ozier A, Dupin I, Trian T, Montaudon M, Laurent F, Marthan R, Berger P. Calcium channel blocker reduces airway remodeling in severe asthma. A proof-of-concept study. Am J Respir Crit Care Med. 2015 Apr 15;191(8):876-83. doi: 10.1164/rccm.201410-1874OC.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Berger, Professor principal investigator
University Hospital Bordeaux, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methoxyverapamil (gallopamil) in people with Asthma, run by University Hospital, Bordeaux at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bronchial smooth muscle remodelling assessed by optic microscopy. (time frame: Before and after 12 months treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00896428, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2013.