Inhaled Glutathione (GSH) Versus Placebo in Cystic Fibrosis

NCT ID: NCT01450267

Last Updated: 2011-10-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2012-12-31

Brief Summary

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.

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Physiological solution

Group Type: PLACEBO_COMPARATOR

Physiological solution

Intervention Type: DRUG

0,13 ml/kg body weight, twice daily, 12 months

Reduced Inhaled Glutathione

Group Type: EXPERIMENTAL

Inhaled Reduced Glutathione

Intervention Type: DRUG

10 mg/kg, twice daily, 12 months

Interventions

Inhaled Reduced Glutathione

10 mg/kg, twice daily, 12 months

Intervention Type: DRUG

Physiological solution

0,13 ml/kg body weight, twice daily, 12 months

Intervention Type: DRUG

Other Intervention Names

GSH; 0,9% sodium chloride sterile solution,

Eligibility 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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University

OTHER

Sponsor Role: collaborator

Serafino A. Marsico

OTHER

Sponsor Role: lead

Responsible Party

Serafino A. Marsico

Professor of Respiratory Diseases

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Serafino A Marsico, PROF

Role: PRINCIPAL_INVESTIGATOR

University of Campania Luigi Vanvitelli

Locations

Ospedale Monaldi, Azienda Ospedaliera Universitaria Federico II

Naples, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

CECILIA CALABRESE, DR

Role: CONTACT

cecilia.calabrese@unina2.it

00390817062365

LIVIA DE PIETRO, DR

Role: CONTACT

depietro.livia@libero.it

00390817062542

Facility Contacts

Valeria Raia, Prof

Role: primary

raia@unina.it

Vincenzo Carnovale, Dr

Role: backup

carnovale@unina.it

References

Griese M, Ramakers J, Krasselt A, Starosta V, Van Koningsbruggen S, Fischer R, Ratjen F, Mullinger B, Huber RM, Maier K, Rietschel E, Scheuch G. Improvement of alveolar glutathione and lung function but not oxidative state in cystic fibrosis. Am J Respir Crit Care Med. 2004 Apr 1;169(7):822-8. doi: 10.1164/rccm.200308-1104OC. Epub 2004 Jan 15.

Reference Type: BACKGROUND

PMID: 14726422 (View on PubMed)

Bishop C, Hudson VM, Hilton SC, Wilde C. A pilot study of the effect of inhaled buffered reduced glutathione on the clinical status of patients with cystic fibrosis. Chest. 2005 Jan;127(1):308-17. doi: 10.1378/chest.127.1.308.

Reference Type: BACKGROUND

PMID: 15653998 (View on PubMed)

Raia V, Maiuri L, Ciacci C, Ricciardelli I, Vacca L, Auricchio S, Cimmino M, Cavaliere M, Nardone M, Cesaro A, Malcolm J, Quaratino S, Londei M. Inhibition of p38 mitogen activated protein kinase controls airway inflammation in cystic fibrosis. Thorax. 2005 Sep;60(9):773-80. doi: 10.1136/thx.2005.042564. Epub 2005 Jun 30.

Reference Type: BACKGROUND

PMID: 15994249 (View on PubMed)

Calabrese C, Tosco A, Abete P, Carnovale V, Basile C, Magliocca A, Quattrucci S, De Sanctis S, Alatri F, Mazzarella G, De Pietro L, Turino C, Melillo E, Buonpensiero P, Di Pasqua A, Raia V. Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis. J Cyst Fibros. 2015 Mar;14(2):203-10. doi: 10.1016/j.jcf.2014.09.014. Epub 2014 Nov 4.

Reference Type: DERIVED

PMID: 25458463 (View on PubMed)

Other Identifiers

FARM7K7XZB

Identifier Type: -

Identifier Source: org_study_id