Major objectives:- To determine the role of small airways abnormalities in the clinical manifestations of asthma;- To evaluate which (combination of) clinical methods best assesses the abnormalities of small airways and large airways disease in…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To determine the role of small airways abnormalities in the clinical
manifestations of asthma.
- To evaluate which (combination of) clinical methods best assess the
abnormalities of small airways and large airways disease in asthma and best
relates to asthma severity, control, and future risk of exacerbations, both
cross-sectionally and longitudinally.
- To assess if a questionnaire (Small Airways Dysfunction Tool) could be
offered to physicians in diagnosing Small Airways Disease (SAD) in asthma, and
thus characterize asthma patients with small airways diseases as determined by
physiologic and radiographic assessments and measurement of specific biomarkers.
Secondary outcome
- To define the physiologic characteristics that correlate with small
airways function in asthma as compared to healthy controls.
- To define the radiographic characteristics that correlate with small airways
function in asthma as compared to healthy controls.
- To determine which direct and indirect measures of inflammation best
correlate with inflammation in the large and small airway compartments.
- To determine if questionnaires such as ACQ-6 and ACT assess small airways
function.
- To determine the correlation between SAD and asthma control.
- To determine if SAD is associated with exacerbations requiring prescription
of oral corticosteroids.
Background summary
the overall hypothesis of this study is that small airways disease (SAD) in
asthma significantly contributes to asthma pathobiology, and measures of small
airways function will correlate with asthma control and exacerbations. To test
this hypothesis, we will recruit 800 subjects with mild, moderate and severe
asthma, and 100 healthy controls (to provide normal reference values for the
study variables). We will follow them longitudinally with periodic assessments
to determine small and large airway function by using physiologic and
radiographic techniques as well as direct and indirect measures of inflammation
above described. We will determine if either of these tests or combination of
tests not only define small airways dysfunction in asthma, but whether SAD
modulates asthma control and risk of exacerbations.
Study objective
Major objectives:
- To determine the role of small airways abnormalities in the clinical
manifestations of asthma;
- To evaluate which (combination of) clinical methods best assesses the
abnormalities of small airways and large airways disease in asthma and best
relates to asthma severity, control, and future risk of exacerbations, both
cross-sectionally and longitudinally;
- To assess if a questionnaire (Small Airways Dysfunction Tool) could be
offered to physicians in diagnosing Small Airways Disease (SAD) in asthma, and
thus characterize asthma patients with small airways diseases as determined by
physiologic and radiographic assessments and measurement of specific
biomarkers.
Study design
This is a multinational, multicentre, non-pharmacological intervention study
made up of a cross-sectional and a longitudinal phase. The Investigator is
directly or indirectly (via GP) responsible for the appropriate individual
treatment for the subject. The assignment of the patient to a particular
therapeutic strategy falls within current practice and the prescription of the
medicine is clearly separated from the decision to include the patient in the
study. The study is not intended to collect information on a single, specific
drug. The prescribed treatment will be reported with the pharmacological name
of each component.
The study plan foresees 3 clinic visits and 2 telephone contacts during a
1-year observation period. Asthmatic patients and healthy controls satisfying
all the inclusion and none of the exclusion criteria will enter the study
cross-sectional phase visit (V1, baseline visit) and the 12-month longitudinal
phase. Follow-up visits to apply the study procedures (see Table 1: Study
Schedule) will take place after 6 (V2) and 12 (V3) months from the
cross-sectional phase visit (V1, baseline visit). In addition, after 3 and 9
months from baseline, all subjects will be contacted by phone calls for the
evaluations described in Table 1. The end of the trial is defined as the last
visit of the last subject in the trial.
Study burden and risks
This study is designed to minimize risk through observance of strict site and
investigator selection criteria, careful subject selection and management.
Drawing blood may cause temporary discomfort from the needle stick, bruising or
infection.
The amount of radiation of the CT scan is very low. Should the patient have
already had many X-Rays, this should be discussed with the doctor.
There are no direct benefits to participate to this study for the patients. The
information gained from the conduct of this study may benefit in the future to
the patients with the same medical conditions.
Via Palermo 26/A
Parma 43122
IT
Via Palermo 26/A
Parma 43122
IT
Listed location countries
Age
Inclusion criteria
Asthmatic patient inclusion criteria
1. Male or female patients aged >= 18 and <= 65 years, who have signed an Informed Consent form prior to initiation of any study-related procedure.
2. Clinical diagnosis of asthma for at least 6 months confirmed by a chest physician according to international guidelines (GINA 2012) supported by objective evidence of any of the following at the baseline visit or in the previous 5 years.
a) Positive response to methacholine challenge test [PC20 < 8 mg/mL or PD20 < 0.7 mg for those subjects not using inhaled corticosteroids (ICS), and PC20 < 16 mg/mL or PD20 < 1.4 mg for subjects using ICS]
or
b) Positive response to a reversibility test, defined as ΔFEV1 >= 12% and >= 200 mL over baseline FEV1, within 30 minutes after administration of 400 µg of salbutamol pMDI administered with or without Spacer
or
c) Peak Flow variability (i.e. highest - lowest PEF over the day/mean value of the two, × 100) > 20%, measured over a follow-up period of 7 days
or
d) Documented response (defined as ΔFEV1 >= 12% and >= 200 mL) after a cycle (e.g., 4 weeks) of regular maintenance anti-asthma treatment.
3. Patients with stable asthma, on any previous regular asthma treatment (*rescue* β2-agonists alone included) at a stable dose, for at least 8 weeks prior to baseline visit.
4. Current smoker, ex-smoker (since the past 12 months) or lifelong non-smoker (total lifetime smoking history < 10 packyears defined as [(number of cigarettes smoked per day) x(number of years of smoking)] / 20).
Healthy subject inclusion criteria
1. Male or female patients aged >= 18 and <= 65 years, who have signed the Informed Consent form prior to initiation of any study-related procedure.
2. No clinical history of asthma or COPD (no respiratory symptoms compatible to asthma or COPD in the past 2 years).
3. Current smoker, ex-smoker (since the past 12 months) or lifelong non-smoker (total lifetime smoking history < 10 packyears).
4. Normal spirometry: baseline FEV1 >= 80% of the predicted normal value, FEV1/FVC > LLN (lower limit of normal).
5. Normal airways responsiveness: PC20 >= 16 mg/mL, PD20 >= 1.4 mg.
Exclusion criteria
Asthmatic patient exclusion criteria
1. Cigarette smoking > 10 packyears defined as [(number of cigarettes smoked per day) x (number of years of smoking)] / 20.
2. diagnosis of COPD confirmed by a chest physician.
3. Asthma exacerbation in the 8 weeks prior to baseline visit (defined as a significant deterioration of asthma and signalled by any or more of the following: need for a systemic corticosteroid course (>= 3 days); hospitalisation for asthma; emergency room attendance for asthma).
4. Clinical or functional uncontrolled respiratory, haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that might, in the judgment of the investigator, compromise the results or interpretation of the study.
5. Pregnant or lactating women (a urine pregnancy test will be performed).
6. Participation in an interventional clinical trial with intake of the last dose of any investigational drug <12 weeks preceding baseline visit (last dose < 5 half-lives prior to baseline visit for biologics).
7. Inability to comply with study procedures.
8. Alcohol or drug abuse.;Healthy subject exclusion criteria
1. Cigarette smoking history > 10 packyears defined as [(number of cigarettes smoked per day) x (number of years of smoking)] / 20.
2. Diagnosed upper and/or lower respiratory disease(s).
3. Clinical or functional uncontrolled haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that might, in the judgment of the investigator, compromise the results or interpretation of the study.
4. Pregnant or lactating women (a urine pregnancy test will be performed).
5. Participation in an interventional clinical trial with intake of the last dose of any investigational drug <12 weeks preceding baseline visit (last dose < 5 half-lives prior to baseline visit for biologics).
6. Inability to comply with study procedures.
7. Alcohol or drug abuse.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02123667 |
| CCMO | NL47847.042.14 |