Inhalation Treatment with Glutathione in Patients with Cystic Fibrosis. A Randomized Clinical Trial

• DOI: 10.1164/rccm.201303-0427oc
• Publication Date: 2013-04-30T12:50:35Z
• Authors: Matthias Griese; Matthias Kappler; Claudia Eismann; Manfred Ballmann; Sibylle Junge; Ernst Rietschel; Silke van Konings...; Doris Staab; Claudia Rolinck-W...; Uwe Mellies; Thomas Köhnlein; Thomas Wagner; Susanne König; Helmut Teschler; Hans-Eberhard Heuer; Matthias Kopp; Susanne Heyder; Jutta Hammermann; Peter Küster; Marguerite Honer; Ulrich Mansmann; Ingrid Beck-Speier; Dominik Hartl; Carola Fuchs; ; Andreas Hector
• Keywords: Glutathione disulfide

Rationale: Glutathione is the major antioxidant in extracellular lining fluid of lungs and depleted patients with cystic fibrosis (CF).Objectives: We aimed to assess glutathione delivered by inhalation as a potential treatment for CF lung disease.Methods: This randomized, double-blind, placebo-controlled trial evaluated inhaled subjects 8 years age older FEV1 40–90% predicted. Subjects were randomized receive 646 mg 4 ml (n = 73) or placebo 80) via an investigational eFlow nebulizer every 12 hours 6 months.Measurements Main Results: (absolute values), both pre–post differences (P 0.180) area under curves 0.205), primary efficacy endpoints, not different between group over 6-month period. Exploratory analysis showed increase from baseline 100 2.2% predicted; this was significant at 3 months, but later. receiving had neither fewer pulmonary exacerbations, nor better scores quality life. Whereas increased metabolites sputum demonstrated delivery lungs, there no indication diminished oxidative stress proteins lipids, evidence anti-inflammatory antiproteolytic actions supplemented airways. The adverse event incidence similar placebo.Conclusions: Inhaled dose administered did demonstrate clinically relevant improvements function, exacerbation frequency, patient-reported outcomes. airways associated changes markers oxidation, proteolysis, inflammation.Clinical registered www.clinicaltrials.gov (NCT00506688) https://eudract.ema.europa.eu/index.html (EudraCT 2005-003870-88).