The majority of cystic fibrosis (CF) patients die from a progressive pulmonary disease.Airway inflammation plays a major role for the pathogenesis of CF lung disease, and ultimately leads to lung destruction. The release of oxidants during the inflammation process leads to a chronic imbalance of oxidants and antioxidants and may be a central component leading to irreversible lung damage in CF patients. The antioxidant glutathione, which is a naturally occurring tripeptide, is depleted in the extracellular epithelial lining fluid of the CF lung. The elevation of reduced level to normal and also the augmentation of glutathione concentrations above the normal level, as observed in smokers and during defence of Pseudomonas infection, may be desirable to avoid lung damage. Data from pilot studies in humans and animals have indicated that the glutathione concentrations in epithelial lining fluid can be elevated by aerosol application. The main objective of this trial is to evaluate the effect of a 24-week treatment with inhaled glutathione compared with control inhalations (normal saline) on pulmonary function in adult and pediatric CF patients. Secondary objectives are to determine the effects of inhaled glutathione on inflammatory variables, glutathione levels and free elastase in induced sputum and to evaluate the safety and tolerability of the 24-week treatment with inhaled GSH. There is considerable hope within the CF community that the addition of anti-oxidative therapy to an already comprehensive program for treating the lungs will decrease morbidity and improve the quality of life for patients with CF.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
153
646 mg GSH-Na powder per vial to prepare a 4ml solution, twice daily for 24 weeks.
4 ml of a 0.9% normal saline solution (9mg/ml NaCl), twice daily for 24 weeks.
Charité Campus Virchow Klinikum,Klinik für Pädiatrie
Berlin, Germany
Universitätskinderklinink
Bochum, Germany
Uniklinik Köln Mukoviszidose Zentrum
Cologne, Germany
Ruhrlandklinink
Essen, Germany
CF-Ambulanz/ Universitätsklinikum Essen
Essen, Germany
CF-Ambulanz Frankfurt
Frankfurt, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, Germany
Gemeinschaftspraxis CF Ambulanz
Hamburg, Germany
Med. Hochschule Hannover
Hanover, Germany
MHH Kinderklinik CF-Ambulanz
Hanover, Germany
...and 4 more locations
Differences between inhaled glutathione and inhaled normal saline with respect to the area under the curve of FEV1 % predicted (forced expiratory volume in 1 second) within the period from baseline to week 24 (V5, EOT)
Time frame: 24 weeks
Treatment changes with respect to the variables:Spirometry,Peak flow,quality-of-life,Weight/ height,Percentage of neutrophils/other cell types (induced sputum),Induced sputum levels of glutathione/ inflammatory mediators,Pulmonary exacerbation
Time frame: 0,4, 12, 24 weeks
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