Bronchiectasis Alpha-1 Augmentation Trial- Modulating Airway Neutrophil Function
- Conditions
- Interventions
- Registration Number
- NCT05582798
- Lead Sponsor
- University of Dundee
- Brief Summary
Double-blind, randomized, cross-over trial involving 20 participants with bronchiectasis.
This trial will make an important contribution to therapeutic development in bronchiectasis by determining whether alpha-1 antitrypsin (AAT) therapy results in reduced airway inflammation and improves neutrophil function.
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- Detailed Description
Bronchiectasis is a debilitating chronic disease associated with a vicious cycle of lung inflammation, infection and failure of mucociliary clearance.
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Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
- Age >18 years
- Bronchiectasis on high resolution computerised tomography (CT) scan affecting 1 or more lobes
- Sputum neutrophil elastase activity greater than or equal to 7 µg/ml on neutrophil elastase assay at the screening visit*
- Daily sputum production as determined by the researcher from the patient's self-report
- Able to provide a sputum sample at the screening and randomization visits either spontaneously
- Ability to give informed consent
- Able to perform all trial procedures with minimal assistance
- Willing to have pregnancy testing, if appropriate
- Severe alpha-1 antitrypsin deficiency (<57 mg/dl in serum) regardless of genotype#
- Immunoglobulin A (IgA) deficient patients with antibodies against IgA
- History of anaphylaxis or other severe systemic reaction to Alpha1-Proteinase Inhibitor
- Primary diagnosis of Chronic Obstructive Pulmonary Disease (COPD) in the opinion of the investigator
- Primary Diagnosis of asthma in the opinion of the investigator
- Active allergic bronchopulmonary aspergillosis, NTM, immunodeficiency or another aetiology of bronchiectasis requiring a specific treatment
- Treatment with antibiotic therapy for an exacerbation of bronchiectasis (other than long term oral or inhaled antibiotics at stable dose) in the 4 weeks prior to randomization
- Cystic fibrosis
- Unstable cardiac disease in the opinion of the investigator
- Congestive cardiac failure and in the opinion of the investigator should not receive iv infusions.
- Traction bronchiectasis due to interstitial lung disease
- Current smoker
- Pregnant or breast feeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Alpha1-Proteinase Inhibitor 180mg/kg Alpha 1-Proteinase Inhibitor 180mg/kg Alpha1-Proteinase Inhibitor 180mg/kg, intravenous infusion, 50mg/ml Alpha1-Proteinase Inhibitor 120mg/kg Alpha 1-Proteinase Inhibitor 120mg/kg Alpha1-Proteinase Inhibitor 180mg/kg, intravenous infusion, 50mg/ml Placebo 2 Sodium chloride Sodium chloride 0.9% volume to match that of Alpha1-Proteinase Inhibitor 120mg/kg, intravenous infusion. Placebo 1 Sodium chloride Sodium chloride 0.9% volume to match that of Alpha1-Proteinase Inhibitor 180mg/kg, intravenous infusion.
- Primary Outcome Measures
Name Time Method To determine the effect of intravenous alpha-1 proteinase inhibitor on sputum neutrophil elastase activity Baseline and 4 weeks Change from baseline in sputum neutrophil elastase activity measured in units/ml
- Secondary Outcome Measures
Name Time Method To determine clinical benefits of alpha-1 proteinase inhibitor Baseline and 4 weeks Spirometry: forced expiratory volume in 1 minute (FEV1); forced vital capacity (FVC); forced expiratory flow 25-75% (FEV25-75); forced expiratory volume in 1 minute/forced vital capacity (FEV1/FVC)
To determine safety and tolerability of intravenous alpha-1 proteinase inhibitor administration 4 weeks Adverse events, serious adverse events and trial treatment withdrawals will be recorded and a comparison made between the 4 treatment groups
To determine the effect of intravenous alpha-1 proteinase inhibitor on neutrophil function Baseline and 4 weeks Sputum neutrophil phagocytosis
Trial Locations
- Locations (1)
NHS Tayside
🇬🇧Dundee, United Kingdom