Efficacy and Safety Study of Inhaled Glutathione in Cystic Fibrosis Patients

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Mukoviszidose Institut gGmbH
ClinicalTrials.gov Identifier:
NCT00506688
First received: July 24, 2007
Last updated: July 6, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Drug: reduced glutathione sodium salt
Drug: 0.9% normal saline (control)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Placebo-controlled, Double-blinded Study to Investigate the Efficacy and Safety of a 24-week Inhalation Treatment With Glutathione in Cystic Fibrosis Patients

Resource links provided by NLM:


Further study details as provided by Mukoviszidose Institut gGmbH:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 153
Study Start Date: July 2007
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: reduced glutathione sodium salt
    646 mg GSH-Na powder per vial to prepare a 4ml solution, twice daily for 24 weeks.
    Other Name: TAD 600
    Drug: 0.9% normal saline (control)
    4 ml of a 0.9% normal saline solution (9mg/ml NaCl), twice daily for 24 weeks.
  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patient, 8 years (pediatric 8 - 17 years inclusive; adult 18 years)
  • Confirmed diagnosis of CF (positive sweat chloride, 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)
  • Patient is able to perform acceptable spirometric maneuvers according to ATS standards
  • FEV1 > 40% predicted and < 90% predicted
  • The patient is clinically stable fulfilling the following:

No evidence of acute upper or lower respiratory tract infection within 4 weeks of screening.

No pulmonary exacerbation requiring an use of i.v./oral/inhaled antibiotics, or oral corticosteroids within 4 weeks of screening.

FEV1 at Visit 2 is within a range of ± 10% of FEV1 from the Visit 1. (If FEV1 at V2 is not within that range, V2 may be re-scheduled once within 7 days)

  • Concomitant or chronic medication is planned to be continued unchanged for the entire study duration
  • The patient or the patient's legally acceptable representative is able to give informed consent in accordance with ICH and GCP guidelines and local legislation
  • Patient is able to comply with the study visit schedule and willing and able to complete the assessments specified in the protocol.

Exclusion Criteria:

  • History of allergy/hypersensitivity (including medication allergy) that is deemed relevant to the trial by the investigator. "Relevance" in this context refers to any increased risk of hypersensitivity reaction to trial medication. (Specific concerns currently identified with respect to the use of inhaled glutathione in allergic patients per se are not existing)
  • 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.
  • Patient with a known relevant substance abuse, including alcohol or drug abuse.
  • Pregnant or lactating woman or female patient of child bearing potential who is sexually active and not using a medically approved form of contraception such as oral or injectable contraceptives, intrauterine devices, double-barrier method, contraceptive patch, male partner sterilization or condoms.
  • Patient with a documented persistent colonization with B. cepacia (defined as more than one positive culture within the past year).
  • Start of a new concomitant or chronic medication for CF within 4 weeks of screening.
  • Existing cycling medication regimen without completion of at least 3 cycles prior to the screening visit or the drug cycles of other therapies are not in accordance with the 4-week time-schedule for the single visits of this study
  • Clinically relevant diseases or medical conditions 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, but is not limited to, significant hematological, hepatic,renal, cardiovascular, and neurological diseases (diabetic patients may participate if their disease is under good control prior to screening).
  • Participation in another study with an investigational drug within one month or 6 halflives(whichever is greater) preceding the screening visit.
  • The patient is an employee of the investigator or the institution with direct involvement in the trial or other trials under the direction of the investigator or their members.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00506688

Locations
Germany
Charité Campus Virchow Klinikum,Klinik für Pädiatrie
Berlin, Germany, 13353
Universitätskinderklinink
Bochum, Germany, 44791
Uniklinik Köln Mukoviszidose Zentrum
Cologne, Germany, D-50924
Ruhrlandklinink
Essen, Germany, 45239
CF-Ambulanz/ Universitätsklinikum Essen
Essen, Germany, D-45128
CF-Ambulanz Frankfurt
Frankfurt, Germany, D-60590
Universitätsklinikum Freiburg
Freiburg, Germany, 79104
Gemeinschaftspraxis CF Ambulanz
Hamburg, Germany, 22763
MHH Kinderklinik CF-Ambulanz
Hannover, Germany, D-30625
Med. Hochschule Hannover
Hannover, Germany, 30625
Universitätsklinik
Leipzig, Germany, 04109
CF-Amulanz/ Dr.von Haunersches Kinderspital
Munich, Germany, D-80337
Klinikum Innenstadt, Medizinische Klinik / Pneumologie
München, Germany, 80336
Clemenshospital GmbH,Akademisches Lehrkrankenhaus der Westfälischen Wildhelms-Universität Münster
Münster, Germany, 48153
Sponsors and Collaborators
Mukoviszidose Institut gGmbH
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Matthias Griese, Prof. Dr. von Haunersches Kinderspital (University of Munich, Germany)
  More Information

No publications provided by Mukoviszidose Institut gGmbH

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mukoviszidose Institut gGmbH
ClinicalTrials.gov Identifier: NCT00506688     History of Changes
Other Study ID Numbers: Muko-D-GSH-4, EudraCT-number: 2005-003870-88
Study First Received: July 24, 2007
Last Updated: July 6, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 24, 2014