None listed
Conditions
Brief summary
People with Chronic Obstructive Pulmonary Disease (COPD) or asthma usually experience swelling (inflammation) in their airways (breathing tubes), that makes is difficult to breathe. This inflammation can worsen their condition and lead to further medical problems. An inflammatory cell called the neutrophil is often present in the airways of people with COPD or asthma, and when activated these cells release molecules that lead to swelling and damage of the lungs. Neutrophils also release ‘extracellular traps’ called NETs, which look like a spider web and are made up of the cell’s DNA (the genetic code which carries all the information about how we look and function) and other inflammatory molecules. These traps can kill bacteria, however if they are not cleared they are toxic to the lungs. We have shown a build-up of NETs in sputum from patients with COPD and asthma. In another lung disease called cystic fibrosis, NETs are broken down and cleared by a treatment called Pulmozyme, which improves lung function and decreases lung attacks. This study will investigate NETs in COPD and asthma, their effects on the lungs, and whether treatment with Pulmozyme can improve symptoms.
Interventions
Participants will attend a screening visit (V1) to assess airway inflammation, and if eligible, a randomisation visit 2 weeks later (V2), All participants deemed eligible for the study, will receive both dornase alfa as well as the placebo medication, which will both be administered via nebulisation. The order in which each medication is received will be randomised and the participant will not be aware of which medication they are receiving at each timepoint. The participant will be randomly all
Participants will attend a screening visit (V1) to assess airway inflammation, and if eligible, a randomisation visit 2 weeks later (V2), All participants deemed eligible for the study, will receive both dornase alfa as well as the placebo medication, which will both be administered via nebulisation. The order in which each medication is received will be randomised and the participant will not be aware of which medication they are receiving at each timepoint. The participant will be randomly allocated to receive either dornase alfa via nebuliser (Pulmozyme, 2.5mg) or placebo, once daily for 10 days. The first treatment sequence will be a period of 10 days (visit 2/3), followed by a 2 week washout period (return for visit 4) and concluding with the second 10 day treatment sequence (visit 5). Participants will be contacted via telephone call midway (Day 5) through each treatment period, to monitor adherence. To further monitor adherence, participants will also be asked to complete a diary and to return all drug ampules (used and unused).
Sponsors
University of Newcastle
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Males and females aged >18 years with Doctor diagnosed stable COPD, confirmed by incompletely reversible airflow obstruction (post bronchodilator FEV1<80% predicted and FEV1/FVC<70%) Males and females aged >18 years with Doctor diagnosed stable asthma Non-smokers or ex-smokers (> 6 months since last cigarette). High levels of sputum NETs (>20ng/uL eDNA, conducted in Aim 1) (determined after screening visit)
Exclusion criteria
COPD or asthma exacerbation or respiratory tract infection (OCS or antibiotics), or change in maintenance therapy in the past 6 weeks (visit will be postponed) Current smoking (last 6 months) Any use of antibiotics in the past month (visit will be postponed) Pregnancy or breastfeeding Inability to attend clinic visits Other significant illness likely to interfere with management or participation in the study Participation in any other interventional research study in the last 4 weeks
Outcome results
None listed