Role of Mitochondria in Non Severe Asthma (MITASTHME)

• ClinicalTrials.gov Identifier: NCT00808730
• Recruitment Status: Completed
• First Posted: December 16, 2008
• Last Update Posted: February 17, 2010
• Sponsor: University Hospital, Bordeaux
• Information provided by: University Hospital, Bordeaux

Tracking Information

• First Submitted Date: December 15, 2008
• First Posted Date: December 16, 2008
• Last Update Posted Date: February 17, 2010
• Study Start Date: February 2009
• Actual Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 15, 2008): BSM mitochondrial biogenesis assessed by the number of mitochondrial sections using electron microscopy, the porin content using western blot, and mitochondrial oxygen consumption evaluated by oxygraphy. [ Time Frame: One bronchial fiberoptic fibroscopy within 15 days after the enrolment ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 15, 2008)

• BSM remodelling assessed by optic microscopy and immunohistochemistry (using anti-alpha smooth muscle actin antibody). [ Time Frame: One bronchial fiberoptic fibroscopy within 15 days after the enrolment ]
• Transcription factors involved in mitochondrial biogenesis assessed by quantitative RT-PCR and western blot. [ Time Frame: One bronchial fiberoptic fibroscopy within 15 days after the enrolment ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Role of Mitochondria in Non Severe Asthma
• Official Title: Role of Mitochondria in Human Bronchial Smooth Muscle Remodeling in Non Severe Asthma
• Brief Summary: Asthma is a frequent disease characterized by bronchial hyperresponsiveness, inflammation and remodelling. Bronchial remodelling is an abnormal repair process that contributes to the development of poorly reversible airway narrowing. It can appear very early in the evolution of the disease and involves an increased mass of bronchial smooth muscle (BSM). The mechanism of such an increase has been related with an increase in smooth muscle cell proliferation. Recently, we have demonstrated that, BSM increased proliferation is induced by an enhanced mitochondrial biogenesis in severe asthma (T. Trian et al. J Exp Med 2007). The objective of this study is to investigate the role of smooth muscle cell mitochondria in non severe asthma

Detailed Description

Bronchial remodelling mainly involves an increased mass of bronchial smooth muscle (BSM), which is related with an increase proliferation of BSM cells. Recently, using BSM cells obtained from severe asthmatics, we have demonstrated that such an increase proliferation was induced by an activation cascade involving an abnormal calcium entry, and the subsequent activation of Calmodulin-kinase IV, PGC-1alpha, NRF-1 and mt-TFA leading to an increase mitochondrial biogenesis (T. Trian et al, J Exp Med 2007). The objective of this study is to investigate the role of BSM cell mitochondria in non severe asthma.

For this purpose, 30 non severe asthmatic adult patients (>18 yr) will be prospectively recruited from the "CHU de Bordeaux" according to the Global Initiative for Asthma (GINA) guidelines. Inclusion visit will include written informed consent, asthma control questionnaire, clinical examination, lung function testing (i.e. arterial gas, exhaled NO, plethysmography), prick tests, chest X Ray and blood sample for total IgE levels. Bronchial specimens will be obtained from all subjects by fiberoptic bronchoscopy. BSM remodelling will be evaluated by morphological analysis. Patients will be divided into 2 groups according to the presence or the absence of BSM remodelling. Using BSM cell culture, the role of mitochondria will be analyzed by electronic microscopy, confocal microscopy, immunoblotting, RT-PCR and oxygraphy.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Health Services Research
• Condition: Asthma

Intervention

Procedure: fiberoptic fibroscopy

Bronchial specimens will be obtained by fiberoptic bronchoscopy within 15 days after the enrolment

Study Arms

Experimental: 1

fiberoptic fibroscopy

Intervention: Procedure: fiberoptic fibroscopy

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.
• Girodet PO, Allard B, Thumerel M, Begueret H, Dupin I, Ousova O, Lassalle R, Maurat E, Ozier A, Trian T, Marthan R, Berger P. Bronchial Smooth Muscle Remodeling in Nonsevere Asthma. Am J Respir Crit Care Med. 2016 Mar 15;193(6):627-33. doi: 10.1164/rccm.201507-1404OC.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 15, 2010): 32
• Original Estimated Enrollment (submitted: December 15, 2008): 30
• Actual Study Completion Date: November 2009
• Actual Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female aged more than 18 years
• Diagnosis of intermittent asthma, mild persistent asthma or moderate persistent according to ATS criteria
• Forced expiratory volume in one second > 60% predicted
• Written informed consent

Exclusion Criteria:

• Smoker or former smoker (tobacco or cannabis)
• Adults protected by law
• Subjects not affiliated with social security
• Subjects during exclusion relative to another protocol or for which the annual maximum allowance of 3800 euros has been reached
• Subject with any co-morbidity (except chronic rhinitis, chronic sinusitis nasal polyps or gastro-oesophageal reflux)
• Asthma exacerbation within 6 weeks before enrolment
• Infections of the upper airway within 3 months before enrolment
• Chronic viral infections (hepatitis, HIV)
• Pregnancy or breastfeeding
• Contraindications to bronchoscopy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00808730
• Other Study ID Numbers: CHUBX 2008/29
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jean-Pierre LEROY / Clinical Research and Innovation Director, University Hospital, Bordeaux
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Bordeaux
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Pierre-Olivier GIRODET, MCU-PH; University Hospital Bordeaux / Département de Pharmacologie, CIC - Université Victor Segalen Bordeaux 2

• PRS Account: University Hospital, Bordeaux
• Verification Date: February 2010