Cystic fibrosis (CF) is the most common autosomal recessive lethal hereditary disorder in Caucasians. The majority of cystic fibrosis patients die as a result of progressive pulmonary disease. Airway inflammation, characterized by an excessive and persistent neutrophilic infiltration, is key for the pathogenesis of CF lung disease, and ultimately leads to lung destruction.
Conditions
Interventions
Product Name: GSH (Glutathione)
Product Code: TAD 600
Pharmaceutical Form: Inhalation vapour, liquid
INN or Proposed INN: Glutathione
Current Sponsor code: GSH
Other descriptive name: reduced glutath
Sponsors
Mukoviszidose Institut gGmbH i. G.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female patients older than 8 years (pediatric 8 – 17 years inclusive; adult older than 18 years) Confirmed diagnosis of CF (positive sweat chloride above 60 mEq/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF phenotype Able to perform acceptable spirometric maneuvers, according to ATS standards FEV1 > 40% predicted and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients with a significant history of allergy/hypersensitivity (including medication allergy) that is deemed relevant to the trial as judged by the Investigator. “Relevance” in this context refers to any increased risk of hypersensitivity reaction to trial medication; there are no specific issues of concern currently identified with respect to use of inhaled glutathione in allergic patients per se Concomitant inhaled thiol-containing medications (e.g., inhaled N-acetylcysteine). Such medication had to be finished at least 2 weeks before the screening visit. Oral N-acetylcysteine may be continued. New oral or inhaled thiol-containing medications (e.g., inhaled or oral N-acetylcysteine) throughout the study period. Patients who have participated in another study with an Investigational drug within one month or 6 half-lives (whichever is greater) preceding the screening visit Patients with known relevant substance abuse, including alcohol or drug abuse. The intention of this criterion is to exclude patients who are considered to be at risk of not complying with or abusing the trial medication administration directives Female patients of child bearing potential who are sexually active and not using a medically approved form of contraception Patients with documented persistent colonization with B. cepacia (defined as more than one positive culture within the past year). The intention of this exclusion criterion is to be consistent with the current policy within the CF community for reducing the risk of B. cepacia cross infection Patients who have started a new chronic medication for CF within 4 weeks of screening. Patients who are on a cycling medication regimen must have completed at least 3 cycles prior to the screening visit and the medication cycles should be in phase with the follow-up appointments Clinically significant disease or medical condition other than CF or CF-related conditions that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data. This includes significant hematological, hepatic, renal, cardiovascular, and neurologic disease. Patients with diabetes may participate if their disease is under good control prior to screening. This criterion provides an opportunity for the investigator to exclude patients based on clinical judgment, even if other egibility criteria are satisfied
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this trial is to determine whether 24 weeks therapy with inhaled glutathione leads to an improvement in FEV1 % predicted in patients with cystic fibrosis (CF), compared to saline control group.;Secondary Objective: Secondary objectives are: To perform a preliminary exploration of the effects of inhaled glutathione on inflammatory variables, i.e. % neutrophils and other cells, free Elastase, Il-8 and myeloperoxidase in induced sputum from the CF patients. Granulocyte and lymphocyte surface markers in sputum will be assessed. To determine the efficacy of inhaled glutathione in terms of other clinical endpoints, including body weight and quality of life. The trial will also evaluate the safety and tolerability of 24 weeks of treatment with inhaled GSH compared with saline inhalations in adult and pediatric CF patients. In certain specialized centers, (in about 60-70 patients), the concentration of glutathione, as well as the cellular differential counts will be determined. ;Primary end point(s): The primary study endpoint to be analyzed statistically is defined as the differences between inhaled glutathione and inhaled normal saline with respect to the absolute change in FEV1 (forced expiratory volume in 1 second) in % predicted between baseline and week 24. Forced expiratory volume in 1 second (FEV1): Spirometry maneuvers Spirometry will be performed according to current ATS recommendations and is to be conducted by appropriately trained laboratory personnel. For each individual patient, spirometry must be conducted by the same technician whenever possible, with the initials of the technician being entered on the CRF; in situations where this is not possible, written justification for using another technician must be provided in the source documents. For individual patients, all spirometry tests should be performed with the same spirometer. | — |
Countries
Germany
Outcome results
None listed