Effect of Montelukast on Remodelling Markers in Asthmatic Children

Overview[ - collapse ][ - ]

Purpose Airway smooth muscle cell layer thickening and sub epithelial fibrosis, key allergen-induced airway remodelling features not modulated by corticosteroids, are reversible by CysLT1 receptor blockade therapy in animals. No data are available, at the present, about the potential effect of LTs receptor antagonists on airway remodelling in asthmatic children. In the present study, the investigators aim to assess whether the addition of montelukast to ICS in mild asthmatic children to inhibit the release of MMP-9, TIMP-1, MMP-12, MMP-9/TIMP1 ratio, procollagen type I C-terminal peptide (PICP) and TGF-beta in the airway fluid collected by induced sputum in asthmatic children. 30-40 atopic children with mild persistent asthma. Children with asthma will be recruited and evaluated with a real life open label trial: they will be randomised into two groups at first visit (T1): 1) group A: in these patients montelukast tablets 5 mg and as needed beta agonist will be administered; 2) group B: in these patients beta agonist therapy only. All children will be evaluated after 8 weeks (T2). They will be tested for lung function, FeNO, metalloproteinase (MMP)-9, MMP-12, tissue inhibitor metalloproteinase-1 (TIMP-1), procollagen type I C-terminal peptide (PICP) and TGF-beta1 levels in sputum.
ConditionAsthma
InterventionDrug: Montelukast
Drug: placebo
PhasePhase 4
SponsorUniversita di Verona
Responsible PartyUniversita di Verona
ClinicalTrials.gov IdentifierNCT00875082
First ReceivedApril 2, 2009
Last UpdatedJune 18, 2013
Last verifiedJune 2013

Tracking Information[ + expand ][ + ]

First Received DateApril 2, 2009
Last Updated DateJune 18, 2013
Start DateFebruary 2010
Estimated Primary Completion DateApril 2013
Current Primary Outcome MeasuresFeNo, Lung Function, MMP-9, MMP-12, TIMP-1, PICP and TGFB determination [Time Frame: 8 weeks] [Designated as safety issue: No]
Current Secondary Outcome MeasuresNot Provided

Descriptive Information[ + expand ][ + ]

Brief TitleEffect of Montelukast on Remodelling Markers in Asthmatic Children
Official TitleEffect of Montelukast on Metalloproteinase (MMP)-9, MMP-12, Tissue Inhibitor Metalloproteinase-1 (TIMP-1), Procollagen Type I C-terminal Peptide (PICP) and TGF-beta1 Levels in Sputum From Mild Intermittent Asthmatic Children: a Pilot Study
Brief Summary
Airway smooth muscle cell layer thickening and sub epithelial fibrosis, key allergen-induced
airway remodelling features not modulated by corticosteroids, are reversible by CysLT1
receptor blockade therapy in animals. No data are available, at the present, about the
potential effect of LTs receptor antagonists on airway remodelling in asthmatic children.

In the present study, the investigators aim to assess whether the addition of montelukast to
ICS in mild asthmatic children to inhibit the release of MMP-9, TIMP-1, MMP-12, MMP-9/TIMP1
ratio, procollagen type I C-terminal peptide (PICP) and TGF-beta in the airway fluid
collected by induced sputum in asthmatic children. 30-40 atopic children with mild
persistent asthma.

Children with asthma will be recruited and evaluated with a real life open label trial: they
will be randomised into two groups at first visit (T1): 1) group A: in these patients
montelukast tablets 5 mg and as needed beta agonist will be administered; 2) group B: in
these patients beta agonist therapy only.

All children will be evaluated after 8 weeks (T2). They will be tested for lung function,
FeNO, metalloproteinase (MMP)-9, MMP-12, tissue inhibitor metalloproteinase-1 (TIMP-1),
procollagen type I C-terminal peptide (PICP) and TGF-beta1 levels in sputum.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
ConditionAsthma
InterventionDrug: Montelukast
Montelukast, chewing tablets 5mg, once daily, 8 weeks
Drug: placebo
placebo chewing tablets once daily, plus inhaled short acting beta2 agonist as needed, 8 weeks
Study Arm (s)
  • Active Comparator: Montelukast
    Montelukast chewing tablets once daily per os, plus inhaled short acting beta2 agonist as needed
  • Placebo Comparator: placebo
    placebo chewing tablets per os once daily, plus inhaled short acting beta 2 agonist as needed

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment30
Estimated Completion DateApril 2013
Estimated Primary Completion DateSeptember 2011
Eligibility Criteria
Inclusion Criteria:

- Diagnostic criteria: the classification of asthma will be based on clinical history
and examination and pulmonary function parameters, according to international
guidelines.

- Stage and/or severity of condition: atopic children with mild intermittent asthma
will be enrolled. Atopy will be evaluated by skin-prick test to common allergens
in the area.

- Confirmatory physical and laboratory findings:

- Age: ranging in age 6 to 14 years.

- Evidence of susceptibility to the disease under study

- Patients have not used ICS during 3-month period prior to study entry

Exclusion Criteria:

- Patients will be excluded if they had used oral steroids in the last month.

- Patients will be excluded if they had acute or chronic lung diseases other than
asthma, upper or lower airway infection in the previous 3 weeks or during the trial,
acute asthma exacerbation, or had used oral steroids in the last month.

- Patients will be excluded if they had acute or chronic lung diseases other than
asthma, upper or lower airway infections in the previous 3 weeks or during the trial,
acute asthma exacerbation, or had used oral steroids in the last month.
GenderBoth
Ages6 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesItaly

Administrative Information[ + expand ][ + ]

NCT Number NCT00875082
Other Study ID NumbersUVAB-02
Has Data Monitoring CommitteeNo
Information Provided ByUniversita di Verona
Study SponsorUniversita di Verona
CollaboratorsNot Provided
Investigators Principal Investigator: Attilio L Boner, MD Pediatric Department, Università di Verona
Verification DateJune 2013

Locations[ + expand ][ + ]

Pediatric Department, University of Verona
Verona, Italy, I-37134