The medical condition is emphysema and will be investigated in subjects with alpha 1-antitrypsin deficiency. MedDRA version: 9.1 Level: LLT Classification code 10001811 Term: Alpha-1 proteinase inhibitor deficiency MedDRA version: 9.1 Level: LLT Classification code 10014563 Term: Emphysema pulmonary MedDRA version: 9.1 Level: LLT
Conditions
Interventions
Trade Name: Prolastin
Product Name: Prolastin
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: alpha 1-proteinase
Sponsors
UHB NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Three subject groups of individuals over the age of 50 years will be studied. Healthy never smokers age 50-70 years, no evidence of lung disease, FEV1>75% predicted, FEV1/VC>70%, no relevant medical or mental disorder, able to give informed consent. Patients with an emphysema COPD phenotype (and normal alpha 1-antitrypsin phenotype), no other active lung disease, FEV1=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Age 80 Continued smoking Frequent or recent acute exacerbations of COPD Other lung disorder Relevant medical or mental illness Diabetes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Neutrophilic inflammation is central to the pathogenesis of emphysema but non-invasive, reproducible methods for measurement have not been available. 18FDG PET / CT is a new imaging method that allows quantitative spatial assessment of lung inflammation and is a potential outcome measure of anti-inflammatory therapy. Alpha 1-antitrypsin augmentation therapy is available in some EU and US states for the modification of emphysema progression in subjects with alpha 1-antitrypsin deficiency. It is proposed to assess the anti-inflammatory efficacy of augmentation therapy in subjects with inherited deficiency and in subjects with usual COPD. Comparison of global lung inflammatory burden will be made between these two groups and normal individuals and the anti-inflammatory efficacy of augmentation therapy will be assessed in subjects with emphysema . ;Secondary Objective: The temporal and spatial relationships between inflammation and emphysema are poorly defined. It will be possible to link 18FDG PET imaging data on inflammation with CT data on emphysema severity and distribution in order to explore the realtionship between causation and morphological change. This will improve understanding of the pathogenesis of emphysema, in particular, whether inflamation occurs in areas of established emphysematous damage, or in lung regions where emphysema cannot yet be demonstrated. In addition, it will be possible to identify whether anti-inflammatory efficacy is influenced by disease stage or emphysema distribution. ;Primary end point(s): Global neutrophilic inflammation within the lung estimated from Patlak plots of 18FDG uptake measured by PET CT imaging. Individual patients will act as their own controls by comparing imaging before and after treatment. Tretament efficacy will be assessed by between group comparison. | — |
Countries
United Kingdom
Outcome results
None listed