The purpose of this study is to assess the anti-inflammatory effects of Indacaterol/glycopyrronium/Mometasone (QVM) 150/50/80 µg once daily versus Indacaterol/Mometasone (QMF) 150/160 µg once daily on the allergen-induced late asthmatic response in…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the reduction in the percentage of sputum eosinophils
24 hours after allergen challenge at the end of each treatment period vs.
control allergen challenge.
Secondary outcome
Change from baseline after allergen challenge of:
• Cell differential counts in blood and sputum 24 hours after allergen
challenge.
• Bronchial and alveolar nitric oxide.
• Multiple Breath Nitrogen Washout (Lung Clearance Index (LCI), Scond, Sacin).
• Lung function (FEV1, FEV1/FVC, FEF25, FEF50, FEF75, FEF25-75).
• Body plethysmography (RV (% predicted), RV/TLC % predicted).
• Impulse Oscillometry. Resistance (R5, R20, R5-20) and Reactance at 5 Hertz
(IOS).
• Genome-wide mRNA and miRNA expression in sputum and in epithelial cells
derived from nasal epithelial brushes.
Background summary
Current treatment for patients with asthma includes inhaled corticosteroids
(ICS) and long-acting β2-agonists (LABA). The long-acting muscarinic antagonist
(LAMA) tiotropium has recently been registered for the treatment of asthma.
Clinical trials have shown beneficial effects on lung function by addition of
tiotropium to standard treatment in moderate and severe asthma. In addition,
treatment with tiotropium reduces the number of severe exacerbations,
suggesting that anticholinergics exerts anti-inflammatory effects in these
patients.
Anti-inflammatory effects of anticholinergics have extensively been
demonstrated in in vitro and in vivo studies using various experimental models.
In vitro, anticholinergics exert direct anti-inflammatory effects on T cells,
macrophages, epithelial cells, and on airway smooth muscle cells. Moreover, in
vivo animal models have demonstrated inhibitory effects of tiotropium or
muscarinic M3 receptor knockout on ovalbumin-induced inflammation, the
anti-inflammatory effects of tiotropium being comparable to those of the
corticosteroid budesonide.
The effects of the combination of anticholinergics with ICS/LABA on airway
inflammation are currently largely unknown. In vitro, it has been shown that
the anticholinergic glycopyrronium acts synergistically with budesonide in
inhibiting tumor necrosis factor α (TNF-α) release from isolated monocytes,
suggesting that the combination of anticholinergics and corticosteroids might
be more effective than the monotherapies in vivo. In addition, we recently
demonstrated that the combination of the anticholinergic tiotropium with the
corticosteroid ciclesonide is more effective than either compound alone in
inhibiting allergen-induced airway inflammation and remodelling in a guinea pig
model of chronic asthma. It is currently unknown whether treatment with
anticholinergics added to ICS/LABA has anti-inflammatory effects in patients
with asthma.
Study objective
The purpose of this study is to assess the anti-inflammatory effects of
Indacaterol/glycopyrronium/Mometasone (QVM) 150/50/80 µg once daily versus
Indacaterol/Mometasone (QMF) 150/160 µg once daily on the allergen-induced late
asthmatic response in patients with asthma.
Study design
Study design: This study will be a double-blind, randomized, two-way cross-over
study.
Study population: A total of 28 patients with mild to moderate severe asthma
(GINA steps 1-3) will be randomized for treatment.
Intervention
Indacaterol/glycopyrronium/Mometasone (QVM) 150/50/80 µg once daily versus
Indacaterol/Mometasone (QMF) 150/160 µg once daily
Study burden and risks
This study has no specific benefits for the participating patients. The study
also has no major risks. Minor risks for participants in this study are:
• Nasal epithelium collection may cause a temporary nose bleed.
• Allergen inhalation can cause dyspnea. After the challenge subjects may take
an inhaled bronchodilator when necessary.
• Blood collection may cause bruising.
• All drugs may cause side effects.
When patients use inhaled corticosteroids and certain types of medication for
asthma (SAMA, B2-agonists + corticosteroids, short-acting B2-agonists +
short-acting anti-cholinergic, theophylline, leukotriene antagonist) at visit
1, they will be asked to stop their inhaled corticosteroid for a short period
of time (4-5 weeks). This is considered to be in mild to moderately severe
asthma (GINA treatment step 1-3). In previous studies stopping the asthma
medication for a short period has never led to serious problems and after the
provocation test and sputum induction every patient will get a bronchodilator.
When lung function has dropped by more than 20% at visit 2 compared to visit 1
(after stopping inhaled corticosteroids), patients will be withdrawn from the
study so they can start using their own medication again.
Hanzeplein 1
Gropningen 9713GZ
NL
Hanzeplein 1
Gropningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
1. Signed informed consent must be obtained prior to participation in the study.
2. Male and female adult patients aged between 18 and 65 years old.
3. Patients with a diagnosis of asthma for at least 6 months prior to Visit 1
with current asthma severity of step 1-3 (GINA 2018).
4. Patients with presence of allergy against house dust mite, cat or grass
pollen.
5. PC20 methacholine <= 8 mg/ml.
6. Drop in FEV1 of 20% or more during the early asthmatic response and drop in
FEV1 of 15% or more during the late asthmatic response, i.e. between 3-8 hours
after allergen challenge.
7. Patients able to produce sputum of sufficient quality for evaluation of cell
differential counts 24 hours after the baseline allergen challenge at Visit 3.
Exclusion criteria
1. Patients who have a smoking history >= 10 pack-years (Note: 1 pack is
equivalent to 20 cigarettes. 10 pack years = 1 pack/day x 10 years or *
pack/day x 20 years). Ex-smokers are eligible for inclusion if they quit
smoking for at least 6 months prior to Visit 1.
2. Patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD).
3. Patients with severe airway obstruction at baseline, FEV1 < 70% of predicted
or < 1.5 liters.
4. Patients who have had an asthma attack/exacerbation requiring systemic
steroids or hospitalization or emergency room visit within 6 weeks of Visit 1.
If patients experience an asthma attack/exacerbation requiring systemic
steroids or hospitalization or emergency room visit, they may be re-screened 6
weeks after recovery from the exacerbation.
5. Patients who have had a respiratory tract infection or clinical significant
asthma worsening as defined by Investigator within 4 weeks prior to Visit 1.
Patients may be re-screened 4 weeks after recovery from their respiratory tract
infection or asthma worsening.
6. Patients who have ever required intubation for a severe asthma
attack/exacerbation.
7. Patients who have a clinical condition which is likely to be worsened by ICS
administration (e.g. glaucoma, cataract and fragility fractures) who are
according to investigator*s medical judgment at risk participating in the study.
8. Patients treated with a LAMA for asthma within 3 months prior to Visit 1.
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2019-001762-14-NL |
| CCMO | NL70842.042.19 |