Cystic FibrosisPhase 3NCT01450267
Inhaled Glutathione (GSH) Versus Placebo in Cystic Fibrosis
A Phase 3 study testing Inhaled Reduced Glutathione and Physiological solution in people with Cystic Fibrosis, run by Serafino A. Marsico at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 to 45 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Inhaled Reduced Glutathione and Physiological solution
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2010to Dec 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Ospedale Monaldi, Azienda Ospedaliera Universitaria Federico II
Naples
Valeria Raia, Prof, raia@unina.it
Vincenzo Carnovale, Dr, carnovale@unina.it
About this study
Official title: Randomized, Single Blind, Controlled Trial of Inhaled Glutathione Versus Placebo in Patients With Cystic Fibrosis
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.
Read the 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
- Being tested
- Inhaled Reduced Glutathione, Physiological solution
- Keywords
- Cystic Fibrosis, Glutathione
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled Reduced GlutathioneDrug
Also called GSH
10 mg/kg, twice daily, 12 months
Physiological solutionDrug
Also called 0,9% sodium chloride sterile solution,
0,13 ml/kg body weight, twice daily, 12 months
| Study group | Role | What they receive |
|---|---|---|
| Physiological solution | Placebo comparator | Not described Receives: Drug: Physiological solution |
| Reduced Inhaled Glutathione | Experimental | Not described Receives: Drug: Inhaled Reduced Glutathione |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (9)
Small airway function
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
Measured: 12 months
Exercise Capacity
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
Measured: 12 months
BMI
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
Measured: 12 months
Dyspnoea
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
Measured: 12 months
Cough
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
Measured: 12 months
Quality of life
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
Measured: 12 months
Pulmonary exacerbations
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
Measured: 12 months
Markers of oxidative stress (H2O2)in serum and in exhaled breath condensate (EBC)
It will be measured at baseline, in the middle and at the end of the study
Measured: 12 months
Epithelial inflammatory markers on brushed nasal epithelial cells
Epithelial tyrosine phosphorylation, p38-MAPK phosphorylation, TNF alfa release will be evaluated at baseline, in the middle and at the end of the study
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2011 (estimated)
- Study startJun 2010
- Primary completionMay 2012 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Serafino A. Marsico
- Sponsor type
- University, hospital or other
- Collaborators
- Federico II University
- Responsible party
- Sponsor-investigator, Serafino A. Marsico, University of Campania Luigi Vanvitelli
- Investigators
- Serafino A Marsico, PROF, Principal investigator, University of Campania Luigi Vanvitelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01450267
- Sponsor's protocol ID
- FARM7K7XZB
- Status last verified
- Oct 2011
- First submitted
- 30 Sep 2011
- Last updated
- 13 Oct 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 14726422Bishop 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.
PubMed 15653998Raia 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.
PubMed 15994249Calabrese 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.
PubMed 25458463
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Single Blind, Controlled Trial of Inhaled Glutathione Versus Placebo in Patients With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT01450267
- Acronym / sponsor ID
- FARM7K7XZB
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, Glutathione
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Serafino A. MarsicoUniversity, hospital or other
- Collaborators
- Federico II University
- Study start
- Jun 2010
- Primary completion
- May 2012 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 12 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Physiological solution | Placebo comparator | Drug: Physiological solution |
| Reduced Inhaled Glutathione | Experimental | Drug: Inhaled Reduced Glutathione |
Who may qualify
- Ages
- 6 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inhaled Reduced GlutathioneAlso: GSH10 mg/kg, twice daily, 12 months | Drug | Reduced Inhaled Glutathione |
| Physiological solutionAlso: 0,9% sodium chloride sterile solution,0,13 ml/kg body weight, twice daily, 12 months | Drug | Physiological solution |
Primary outcome
Forced expiratory volume in one second (FEV1) percent
Time frame: 12 months
Increase of at least 15% of the percent of forced expiratory volume in one second (FEV1) after GSH therapy compared to placebo
9 secondary outcomes
Small airway function
Time frame: 12 months
Exercise Capacity
Time frame: 12 months
BMI
Time frame: 12 months
Dyspnoea
Time frame: 12 months
Cough
Time frame: 12 months
Quality of life
Time frame: 12 months
Pulmonary exacerbations
Time frame: 12 months
Markers of oxidative stress (H2O2)in serum and in exhaled breath condensate (EBC)
Time frame: 12 months
Epithelial inflammatory markers on brushed nasal epithelial cells
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2011.
- Background: PubMed 14726422Griese 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.
- Background: PubMed 15653998Bishop 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.
- Background: PubMed 15994249Raia 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.
- Derived from this study: PubMed 25458463Calabrese 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Serafino A Marsico, PROF principal investigator
University of Campania Luigi Vanvitelli
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Inhaled Reduced Glutathione and Physiological solution in people with Cystic Fibrosis, run by Serafino A. Marsico at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact CECILIA CALABRESE, DR (00390817062365, cecilia.calabrese@unina2.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forced expiratory volume in one second (FEV1) percent (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01450267, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2011.