Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study

May 5, 2014 updated by: Alberto Papi, MD, Università degli Studi di Ferrara

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 4

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

  • Germany
      • Grosshansdorf, Germany, 22927
        • Hospital Grosshansdorf
  • Italy
      • Ferrara, Italy, 44121
        • Research Centre on Asthma and COPD, University of Ferrara

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 to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

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

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
slope of phase III (dN2) by nitrogen single breath test
Time Frame: At baseline
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
At baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Closing volume and closing capacity by nitrogen single breath test (NSBT)
Time Frame: At baseline
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.
At baseline
Respiratory Resistance by oscillometry technique
Time Frame: At baseline
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.
At baseline
Lung volumes
Time Frame: At baseline
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.
At baseline
Asthma control
Time Frame: At baseline
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.
At baseline
Correlations between small airway functional parameters and asthma control scores
Time Frame: At baseline
To evaluate at baseline correlations between parameters related to asthma control (questionnaire scores, symptoms and use of rescue medications) and functional measurements
At baseline
Changes after extrafine intervention
Time Frame: Change at 3 months vs baseline
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.
Change at 3 months vs baseline

Collaborators and Investigators

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

Sponsor

Università degli Studi di Ferrara

Collaborators

Chiesi Farmaceutici S.p.A.

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

November 1, 2011

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

May 9, 2012

First Submitted That Met QC Criteria

June 14, 2012

First Posted (Estimate)

June 15, 2012

Study Record Updates

Last Update Posted (Estimate)

May 6, 2014

Last Update Submitted That Met QC Criteria

May 5, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAISA01

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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