Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study

This study has been completed.
Sponsor:
Collaborator:
Chiesi Farmaceutici S.p.A.
Information provided by (Responsible Party):
Alberto Papi, MD, Università degli Studi di Ferrara
ClinicalTrials.gov Identifier:
NCT01620099
First received: May 9, 2012
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

Asthma is an inflammatory disease affecting the whole respiratory system, from central to peripheral airways. Anti-inflammatory treatment with inhaled corticosteroids (ICS), with or without long-acting β2-adrenoceptor agonists (LABA), is the cornerstone of asthma management [GINA Guideline - available at www.ginasthma.com]. Nevertheless, a considerable subset of asthmatic patients neither benefits from ICS nor gain optimal asthma control even with ICS/LABA combinations.

The involvement of the distal lung, i.e. the peripheral membranous bronchioles < 2 mm in diameter (so-called small airways), in the pathogenesis of asthma has been extensively investigated and its significance debated. However, whether specifically targeting distal lung abnormalities can lead to further clinical benefit is still an open question. In this context, interest has been raised by hydrofluoroalkane (HFA) pressurised metered-dose inhalers, which can deliver compounds with a mass median aerodynamic diameter that is significantly smaller than other available devices, leading to increase peripheral airways drug deposition.

Up to 30% of asthmatic patients smoke, mirroring the rate found in the general population. Several data document that smoking habit negatively affect corticosteroid efficacy in asthma. In particular, asthmatic patients who smoke experience faster lung function decline, increased frequency of exacerbations and reduced asthma control despite being regularly treated. Several molecular mechanisms have been proposed to address the issue of reduced corticosteroids responsiveness in smoker patients. However it has been never investigated whether reduced corticosteroid responsiveness in asthmatic patients who smoke can be related to more severe small airways involvement leading to impaired distribution or impaired peripheral deposition of inhaled corticosteroids. If this is the case, asthmatic patients who smoke might benefit from a pharmacological approach able to target and to reach small airways.


Condition Intervention Phase
Asthma
Drug: Extrafine treatment (Clenilexx(R) or Foster(R))
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study

Resource links provided by NLM:


Further study details as provided by Università degli Studi di Ferrara:

Primary Outcome Measures:
  • slope of phase III (dN2) by nitrogen single breath test [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    The primary outcome will measure and compare at baseline slope of phase III (dN2) by nitrogen single breath test (NSBT) between asthmatic who smoke and asthmatic who do not smoke matched for age, gender and % predicted FEV1


Secondary Outcome Measures:
  • Closing volume and closing capacity by nitrogen single breath test (NSBT) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    To evaluate and compare at baseline other nitrogen single breath test measures including closing volume and closing capacity in asthmatic who smoke and asthmatic who do not smoke matched for age, gender and % predicted FEV1.

  • Respiratory Resistance by oscillometry technique [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    To evaluate differences in mean resistive component of respiratory impedence (Rrs) and resistance at different frequency (Rr0, Rr5, Rr20) by forced oscillometry technique (FOT) at baseline between asthmatics who smoke compared to asthmatics who do not smoke matched for age, gender and % predicted FEV1.

  • Lung volumes [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    To evaluate differences in forced vital capacity (FVC), slow vital capacity/forced vital capacity ratio (SVC/FVC), residual volume (RV) and total lung capacity (TLC) at baseline between asthmatics who smoke compared to asthmatics who do not smoke matched for age, gender and % predicted FEV1.

  • Asthma control [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    To evaluate differences in parameters related to asthma control (Asthma Control Test scores, use of rescue medications) at baseline between asthmatics who smoke compared to asthmatics who do not smoke matched for age, gender and % predicted FEV1.

  • Correlations between small airway functional parameters and asthma control scores [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    To evaluate at baseline correlations between parameters related to asthma control (questionnaire scores, symptoms and use of rescue medications) and functional measurements

  • Changes after extrafine intervention [ Time Frame: Change at 3 months vs baseline ] [ Designated as safety issue: No ]
    To evaluate changes in functional parameters and parameters related to asthma control in asthmatic patients who smoke compared to asthmatic patients who do not smoke after a 3-months extrafine inhaled treatment.


Estimated Enrollment: 60
Study Start Date: November 2011
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Asthmatic nonsmokers
Asthmatic patients aged 18-50 years old, at stage 2-3 according to GINA international guidelines, on inhaled treatment (ICS alone or combination ICS/LABA) other than extrafine formulations, will be enrolled. This group includes patients who never smoked. Following the initial evaluation (cross-sectional - primary outcome) patients will be switched to an extrafine equipotent dose of the same compound (BDP-HFA if the patient was on ICS) or combination (BDP-HFA/F if the patient was on ICS/LABA combination). After 3-months patients will be reassessed for lung function and asthma control
Drug: Extrafine treatment (Clenilexx(R) or Foster(R))
Following the initial evaluation (cross-sectional) patients will be switched to an extrafine equipotent dose of the same compound (extrafine beclomethasone dipropionate - Clenilexx(R) - if the patient was on ICS) or combination (extrafine beclomethasone dipropionate/formoterol - Foster(R) - if the patient was on ICS/LABA combination). After 3-months patients will be reassessed for lung function and asthma control
Active Comparator: Asthmatic smokers
Asthmatic patients aged 18-50 years old, at stage 2-3 according to GINA international guidelines, on inhaled treatment (ICS alone or combination ICS/LABA) other than extrafine formulations, will be enrolled. This group includes patients who smoked with a smoking habit ranging from 10 to 20 pack/years. Following the initial evaluation (cross-sectional - primary outcome) patients will be switched to an extrafine equipotent dose of the same compound (BDP-HFA if the patient was on ICS) or combination (BDP-HFA/F if the patient was on ICS/LABA combination). After 3-months patients will be reassessed for lung function and asthma control
Drug: Extrafine treatment (Clenilexx(R) or Foster(R))
Following the initial evaluation (cross-sectional) patients will be switched to an extrafine equipotent dose of the same compound (extrafine beclomethasone dipropionate - Clenilexx(R) - if the patient was on ICS) or combination (extrafine beclomethasone dipropionate/formoterol - Foster(R) - if the patient was on ICS/LABA combination). After 3-months patients will be reassessed for lung function and asthma control

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients aged 18-50 years old, at stage 2-3 according to GINA international guidelines
  • patients must be free from an exacerbation from at least 2 months
  • patients must be on inhaled treatment (ICS alone or combination ICS/LABA) other than extrafine formulations from at least 3 months.
  • according to smoking habit, patients will be divided in two groups:

    1. nonsmokers: patients who never smoked
    2. smokers: patients with a smoking habit ranging from 10 to 20 pack/years.

Exclusion Criteria:

  • to avoid possible overlapping with chronic obstructive pulmonary disease, patients will not be included in the study if any of the following exclusion criteria are present:

    • aged > 50 years
    • heavy-smoker patients (pack/years > 20)
    • patients with a not fully reversible airflow obstruction (i.e. post-bronchodilator FEV1/FVC < 70%)
    • patients with an impaired diffusion capacity (DLCO < 80%v predicted).
  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: NCT01620099

Locations
Germany
Hospital Grosshansdorf
Grosshansdorf, Germany, 22927
Italy
Research Centre on Asthma and COPD, University of Ferrara
Ferrara, Italy, 44121
Sponsors and Collaborators
Università degli Studi di Ferrara
Chiesi Farmaceutici S.p.A.
Investigators
Principal Investigator: Alberto Papi, MD Università degli Studi di Ferrara
  More Information

Publications:

Responsible Party: Alberto Papi, MD, Professor, Università degli Studi di Ferrara
ClinicalTrials.gov Identifier: NCT01620099     History of Changes
Other Study ID Numbers: SAISA01
Study First Received: May 9, 2012
Last Updated: May 5, 2014
Health Authority: Italy: National Institute of Health

Keywords provided by Università degli Studi di Ferrara:
Asthma
Cigarette smoke
Small airways
Lung function
Asthma control

ClinicalTrials.gov processed this record on September 29, 2014