Bronchiectasis Alpha-1 Augmentation Trial- Modulating Airway Neutrophil Function

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.
...

Detailed Description

Bronchiectasis is a debilitating chronic disease associated with a vicious cycle of lung inflammation, infection and failure of mucociliary clearance.
...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
20
Inclusion Criteria
  • 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
Read More
Exclusion Criteria
  • 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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Alpha1-Proteinase Inhibitor 180mg/kgAlpha 1-Proteinase Inhibitor 180mg/kgAlpha1-Proteinase Inhibitor 180mg/kg, intravenous infusion, 50mg/ml
Alpha1-Proteinase Inhibitor 120mg/kgAlpha 1-Proteinase Inhibitor 120mg/kgAlpha1-Proteinase Inhibitor 180mg/kg, intravenous infusion, 50mg/ml
Placebo 2Sodium chlorideSodium chloride 0.9% volume to match that of Alpha1-Proteinase Inhibitor 120mg/kg, intravenous infusion.
Placebo 1Sodium chlorideSodium chloride 0.9% volume to match that of Alpha1-Proteinase Inhibitor 180mg/kg, intravenous infusion.
Primary Outcome Measures
NameTimeMethod
To determine the effect of intravenous alpha-1 proteinase inhibitor on sputum neutrophil elastase activityBaseline and 4 weeks

Change from baseline in sputum neutrophil elastase activity measured in units/ml

Secondary Outcome Measures
NameTimeMethod
To determine clinical benefits of alpha-1 proteinase inhibitorBaseline 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 administration4 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 functionBaseline and 4 weeks

Sputum neutrophil phagocytosis

Trial Locations

Locations (1)

NHS Tayside

🇬🇧

Dundee, United Kingdom

© Copyright 2024. All Rights Reserved by MedPath