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Inhaled Glutathione (GSH) Versus Placebo in Cystic Fibrosis

This study is currently recruiting participants.
Verified October 2011 by Second University of Naples
Sponsor:
Collaborator:
Federico II University
Information provided by (Responsible Party):
Serafino A. Marsico, Second University of Naples
ClinicalTrials.gov Identifier:
NCT01450267
First received: September 30, 2011
Last updated: October 12, 2011
Last verified: October 2011
History of Changes
  Purpose

Cystic fibrosis (CF) is the most common inherited disease among the Caucasian population with considerable morbidity and reduced life expectancy.

Excessive oxidants released by activated inflammatory cells and persisting infections are considered the main mechanism of damage of respiratory epithelium in CF.Glutathione (GSH) represents the first-line defence of the lung against oxidative stress-induced cell injury; however, a depletion of its levels has been observed in the airways of patients affected by CF. In vitro studies have showed that CFTR protein plays a pivotal role in transmembrane glutathione transport. Therapeutic approaches with inhaled GSH could improve the reduced lung antioxidant capacity in order to counterbalance the oxidant stress linked to the chronic airway inflammation and bacterial infection.

Primary objective of the study is to investigate whether a 12 months treatment with inhaled GSH can improve airway obstruction in CF patients. Secondary objectives include the effects of GSH therapy on exercise capacity, body mass index (BMI), respiratory symptoms, quality of life, frequency of pulmonary exacerbations, hospital admissions, and antibiotic administration. Moreover the study will evaluate the effect of GSH therapy on markers of oxidative stress in exhaled breath condensate (EBC) and in serum, and on inflammatory markers on brushed nasal epithelial cells.


Condition Intervention Phase
Cystic Fibrosis
 Drug: Inhaled Reduced Glutathione
Drug: Physiological solution
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Randomized, Single Blind, Controlled Trial of Inhaled Glutathione Versus Placebo in Patients With Cystic Fibrosis

Resource links provided by NLM:

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Glutathione
U.S. FDA Resources

Further study details as provided by Second University of Naples:

Primary Outcome Measures:
  • Forced expiratory volume in one second (FEV1) percent [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Increase of at least 15% of the percent of forced expiratory volume in one second (FEV1) after GSH therapy compared to placebo


Secondary Outcome Measures:
  • Small airway function [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    It will be assessed by the flow volume curve and it will bealso evaluated after 1,3,6,and 9 months from the beginning of the treatments and after 1, 3, and 6 months from the end of the treatments

  • Exercise Capacity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    It will be measured by the six minutes walking test and it will be also evaluated after 1,3,6, and 9 months from the beginning of the treatments and after 1, 3, and 6 months from the end of the treatments

  • BMI [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    It will be also evaluated after 1,3,6, and 9 months from the beginning of the treatments and after 1, 3, and 6 months from the end of the treatments

  • Dyspnoea [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    It will be assessed through the Modified Medical Research Council (MMRC) dyspnoea scale and it will be also evaluated after 1,3,6, and 9 months from the beginning of the treatments and after 1, 3, and 6 months from the end of the treatments

  • Cough [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    It will be assessed by the Chronic Cough Impact Questionnaire (CCIQ)and it will be also evaluated after 1,3,6, and 9 months from the beginning of the treatments and after 1, 3, and 6 months from the end of the treatments

  • Quality of life [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    It will be assessed according to Cystic Fibrosis Quality of Life Questionnaire (CFQoL) (not for children 6-13 years old)and it will be also evaluated after 1,3,6, and 9 months from the beginning of the treatments and after 1, 3, and 6 months from the end of the treatments

  • Pulmonary exacerbations [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    It will be assessed evaluating the hospital admissions and antibiotic administrations. It will be also evaluated after 1,3,6, and 9 months from the beginning of the treatments and after 1, 3, and 6 months from the end of the treatments

  • Markers of oxidative stress (H2O2)in serum and in exhaled breath condensate (EBC) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    It will be measured at baseline, in the middle and at the end of the study

  • Epithelial inflammatory markers on brushed nasal epithelial cells [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Epithelial tyrosine phosphorylation, p38-MAPK phosphorylation, TNF alfa release will be evaluated at baseline, in the middle and at the end of the study


Estimated Enrollment: 150
Study Start Date: June 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Physiological solution Drug: Physiological solution
0,13 ml/kg body weight, twice daily, 12 months
Other Name: 0,9% sodium chloride sterile solution,
Experimental: Reduced Inhaled Glutathione Drug: Inhaled Reduced Glutathione
10 mg/kg, twice daily, 12 months
Other Name: GSH

Detailed Description:

150 eligible patients will be enrolled on the basis of inclusion criteria. Patients will be divided in two groups: 1) Group 1 age between 6 and 18 years; 2) Group 2 older than 18 years. Patients will be randomly assigned to the treatment or placebo arm.Patients randomized in the GSH arm will receive a dosage of 10 mg/kg bid over a 12 months period.

Clinical visits will take place at the beginning (visit 0, enrolment visit) and after one month (visit 1), three months (visit 2), six months (visit 3) nine months (visit 4), and twelve months (visit 5, end of treatments).

Follow-up clinical visits will take place one month (visit 6), three months (visit 7), six months (visit 8) after the end of treatments.

At visit 0, all eligible patients will inhale GSH (10 mg/Kg) and a dynamic spirometry will be performed before, 10 and 60 minutes after inhalation. Patients showing a decrease in FEV1 greater than 15% after GSH inhalation will be excluded from the study.

At visit 0 and at each following visits (visit 1, 2, 3, 4, 5, 6, 7 and 8) will be performed and evaluated:

  • Physical examination, measurement of vital signs, body temperature,BMI,and Spirometry;
  • 6 minute walking test;
  • MMRC dyspnoea scale;
  • Chronic cough impact questionnaire;
  • Cystic Fibrosis Quality of Life Questionnaire;
  • Number of pulmonary exacerbations;
  • Number and duration of hospital admissions for pulmonary exacerbations;
  • Number, duration and route of administration of antibiotics;
  • Blood sampling for haematological and biochemical analysis;
  • Brushing of nasal epithelial cell, exhaled breath condensate with evaluation of markers of oxidative stress (H2O2), and blood sample for the measurement of markers of oxidative stress in serum will be performed in a subgroup of patients at visits 0, 3, and 5.
  Eligibility

Ages Eligible for Study:   6 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • a confirmed diagnosis of cystic fibrosis documented by sweat chloride test over 60 mmol/L and/or genotype analysis;
  • male and female aged older than 6 years;
  • stable clinical condition;
  • written informed consent.

Exclusion Criteria:

  • pregnancy and fertile women taking oral contraceptives;
  • cigarette smoking;
  • positive culture for Burkholderia Cepacia;
  • history of haemoptysis or pneumothorax;
  • FEV1<= 40% of the predicted value;
  • hyperresponsiveness to GSH inhalation test.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01450267

Contacts
Contact: CECILIA CALABRESE, DR 00390817062365 cecilia.calabrese@unina2.it
Contact: LIVIA DE PIETRO, DR 00390817062542 depietro.livia@libero.it

Locations
Italy
Ospedale Monaldi, Azienda Ospedaliera Universitaria Federico II Recruiting
Naples, Italy
Contact: Valeria Raia, Prof         raia@unina.it    
Contact: Vincenzo Carnovale, Dr         carnovale@unina.it    
Principal Investigator: Cecilia Calabrese, Dr            
Sponsors and Collaborators
Serafino A. Marsico
Federico II University
Investigators
Principal Investigator: Serafino A Marsico, PROF Second University of Naples
  More Information

Additional Information:
AIFA website of clinical experimentations  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: Serafino A. Marsico, Professor of Respiratory Diseases, Second University of Naples
ClinicalTrials.gov Identifier: NCT01450267     History of Changes
Other Study ID Numbers: FARM7K7XZB
Study First Received: September 30, 2011
Last Updated: October 12, 2011
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Second University of Naples:
Cystic Fibrosis
Glutathione

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 May 19, 2013