Inhaled Glutathione (GSH) Versus Placebo in Cystic Fibrosis

NCT01450267 | Unknown Phase 3 DMC

• 1 other identifier: FARM7K7XZB
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Glutathione

Outcome Measures

Primary Outcomes (1)

• Forced expiratory volume in one second (FEV1) percent

  Increase of at least 15% of the percent of forced expiratory volume in one second (FEV1) after GSH therapy compared to placebo

  12 months

Secondary Outcomes (9)

• Small airway function

  12 months

• Exercise Capacity

  12 months

• BMI

  12 months

• Dyspnoea

  12 months

• Cough

  12 months

Study Arms (2)

Physiological solution

PLACEBO COMPARATOR

Drug: Physiological solution

Reduced Inhaled Glutathione

EXPERIMENTAL

Drug: Inhaled Reduced Glutathione

Interventions

Inhaled Reduced Glutathione DRUG

10 mg/kg, twice daily, 12 months

Also known as: GSH

Reduced Inhaled Glutathione

Physiological solution DRUG

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

Also known as: 0,9% sodium chloride sterile solution,

Physiological solution

Eligibility Criteria

• Age: 6 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Serafino A. Marsico: lead
• Federico II University: collaborator

Study Sites (1)

Ospedale Monaldi, Azienda Ospedaliera Universitaria Federico II

Naples, Italy

RECRUITING

Related Publications (4)

• 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.

  PMID: 14726422 BACKGROUND

• 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.

  PMID: 15653998 BACKGROUND

• 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.

  PMID: 15994249 BACKGROUND

• 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.

  PMID: 25458463 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Serafino A Marsico, PROF

  University of Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CECILIA CALABRESE, DR

CONTACT

00390817062365; cecilia.calabrese@unina2.it

LIVIA DE PIETRO, DR

CONTACT

00390817062542; depietro.livia@libero.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Respiratory Diseases

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 12, 2011
• Study Start: June 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: December 1, 2012
• Last Updated: October 13, 2011

Record last verified: 2011-10

Locations

IT (1)