Cystic FibrosisPhase 2NCT02276898
A Randomized-Controlled Trial of Inhaled Hypertonic Saline (7%) to Evaluate the Lung Clearance Index
A Phase 2 study testing Hypertonic Saline 7% in people with Cystic Fibrosis, run by The Hospital for Sick Children at 2 sites in Canada.
Trial summary
The Lung Clearance Index (LCI) is a non invasive measure of lung function that is more sensitive than FEV1. It can be used to measure lung function in children younger than 6 years of age. Therefore, it has a future role in assessing novel therapeutics in the Cystic Fibrosis (CF) population. Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Hypertonic Saline 7%
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 2 sitesCanada
- Study dates
- Nov 2011to Sep 2014
- Phase
- Phase 2
- 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 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
- Informed consent and verbal assent (as appropriate) provided by the subject's parent or legal guardian and the subject
- At least six years of age at enrolment
- Able to perform reproducible spirometry meeting American Thoracic Society standards
- Pre-bronchodilator FEV1 % predicted > or equal to 40 % predicted
- Ability to perform a reproducible LCI maneuver at screening
Who cannot join
- Known respiratory culture positive for Burkholderia cepacia
- Previous lung transplantation
- Use of intravenous antibiotics within 14 days of screening
- Use of oral antibiotics including prophylactic antibiotics (e.g., augmentin, tetracycline, cloxacillin, cephalosporins, septra, bactrim) within 14 days of screening
- Initiation of a new maintenance (e.g high dose ibuprofen, Pulmozyme®, aerosolized antibiotics) within 14 days of screening
- Use of systemic corticosteroids within 14 days of screening
Show all 11Show fewer
- Investigational drug use within 30 days of screening
- Use of hypertonic saline (7%) < 4 weeks before screening or outside of the study protocol
- Participation in any therapeutic clinical study <4 weeks or, 5 half-lives, whichever is longer, before screening
- Smoking < 3 months before screening
- Presence of a condition or abnormality that in the opinion of the site investigator would compromise the safety of the subject or the quality of the data
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
The Hospital for Sick Children
Toronto, Ontario, M5V1X8
St. Michaels Hospital
Toronto, Ontario
About this study
Official title: A Randomized-Controlled Trial of Inhaled Hypertonic Saline (7%) to Evaluate the Lung Clearance Index as a Short-term Pharmacodynamic Biomarker in Patients With Cystic Fibrosis.
The Lung Clearance Index (LCI) is a non invasive measure of lung function that is more sensitive than FEV1. It can be used to measure lung function in children younger than 6 years of age. Therefore, it has a future role in assessing novel therapeutics in the Cystic Fibrosis (CF) population. As such, determining if it can be used as a short term pharmacodynamic biomarker is paramount.
Read the detailed description
Inhaled Hypertonic saline (7%) is a treatment intervention for Cystic Fibrosis patients and has previously been shown to improve lung function and decrease the number of pulmonary exacerbations. The Cystic Fibrosis Transmembrane Regulator Gene (CFTR) protein is essential for maintaining fluid and electrolyte homeostasis in the lung and CFTR defects cause depletion of the periciliary liquid layer which results in impaired mucociliary clearance. Inhaled hypertonic saline (7%) acts as an osmotic agent in the lungs; it repletes the airway surface liquid (ASL) and improves mucociliary clearance.
In addition, we have recently demonstrated that the Lung Clearance Index (LCI) is also a responsive outcome measure. In an intervention study in which patients were treated with hypertonic saline inhalation twice daily for 28 days, LCI but not FEV1 significantly improved in 17 pediatric Cystic Fibrosis (CF) patients with mild lung disease. In this study, LCI was more sensitive to a change in response to treatment than spirometry in a small number of patients. However, it still remains unknown if the LCI will be able to detect a treatment effect on a shorter time scale after an intervention. Its use as a short-term pharmacodynamic biomarker in CF patients remains unknown. The ability of the LCI to detect treatment effects within hours after an intervention would be invaluable to the development of new therapeutic interventions for CF patients.
- Conditions
- Cystic Fibrosis
- Being tested
- Hypertonic Saline 7%, Isotonic Saline 0.9% (Placebo)
- Keywords
- pediatric, lung clearance index, Multiple Breath Washout, Hypertonic Saline
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypertonic Saline 7%Drug
PARI Hyper-Sal™ Sodium Chloride Solution - 7%
Isotonic Saline 0.9% (Placebo)Drug
| Study group | Role | What they receive |
|---|---|---|
| Hypertonic Saline | Active comparator | The treatment intervention is 1 inhalation of 7% hypertonic saline (4ml) Receives: Drug: Hypertonic Saline 7% |
| Isotonic Saline | Placebo comparator | The placebo intervention is 1 inhalation of 0.9% isotonic saline Receives: Drug: Isotonic Saline 0.9% (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lung Clearance Index
The change in the Lung Clearance Index as measured by nitrogen washout between baseline and 24 hours after each inhalation of Hypertonic Saline (7%) and Isotonic Saline (0.9%)
Measured: Baseline to 24 hrs post dose
Secondary outcomes (3)
Pulmonary Function Testing
Forced Expiratory Volume in one second (FEV1) % predicted, Forced Expiratory Vital Capacity (FVC) % predicted and Forced Expiratory Flow rate (FEF) 25-75 % predicted will be measured using spirometry.
Measured: Baseline, 1,2,4 and 24hrs post-dose
Lung Clearance Index measured using Mass Spectroscopy
The multiple breath washout will be performed in the classical method using a mass spectroscopy (MS): each test consists of two phases: a wash-in phase and washout phase using an inert dry gas mixture containing 4% Sulfur hexafluoride (SF6), 4% He, 21% oxygen and balance nitrogen.
Measured: Baseline, 1,2,4 and 24 hrs post dose
Lung Clearance Index measured using Nitrogen Washout
The change in the Lung Clearance Index as measured by nitrogen washout between baseline and 1,2 and 4 hours after each inhalation of Hypertonic Saline (7%) and Isotonic Saline (0.9%)
Measured: Baseline, 1,2, 4hrs post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2014 (estimated)
- Study startNov 2011
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Reshma Amin, The Hospital for Sick Children
- Investigators
- Reshma Amin, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02276898
- Sponsor's protocol ID
- 1000024909
- Status last verified
- May 2015
- First submitted
- 22 Oct 2014
- Last updated
- 22 May 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized-Controlled Trial of Inhaled Hypertonic Saline (7%) to Evaluate the Lung Clearance Index as a Short-term Pharmacodynamic Biomarker in Patients With Cystic Fibrosis.
- ClinicalTrials.gov ID
- NCT02276898
- Acronym / sponsor ID
- 1000024909
- Conditions
- Cystic Fibrosis
- Keywords
- pediatric, lung clearance index, Multiple Breath Washout, Hypertonic Saline
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 28 Oct 2014 (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.
The Lung Clearance Index (LCI) is a non invasive measure of lung function that is more sensitive than FEV1. It can be used to measure lung function in children younger than 6 years of age. Therefore, it has a future role in assessing novel therapeutics in the Cystic Fibrosis (CF) population. As such, determining if it can be used as a short term pharmacodynamic biomarker is paramount.
Detailed description
Inhaled Hypertonic saline (7%) is a treatment intervention for Cystic Fibrosis patients and has previously been shown to improve lung function and decrease the number of pulmonary exacerbations. The Cystic Fibrosis Transmembrane Regulator Gene (CFTR) protein is essential for maintaining fluid and electrolyte homeostasis in the lung and CFTR defects cause depletion of the periciliary liquid layer which results in impaired mucociliary clearance. Inhaled hypertonic saline (7%) acts as an osmotic agent in the lungs; it repletes the airway surface liquid (ASL) and improves mucociliary clearance.
In addition, we have recently demonstrated that the Lung Clearance Index (LCI) is also a responsive outcome measure. In an intervention study in which patients were treated with hypertonic saline inhalation twice daily for 28 days, LCI but not FEV1 significantly improved in 17 pediatric Cystic Fibrosis (CF) patients with mild lung disease. In this study, LCI was more sensitive to a change in response to treatment than spirometry in a small number of patients. However, it still remains unknown if the LCI will be able to detect a treatment effect on a shorter time scale after an intervention. Its use as a short-term pharmacodynamic biomarker in CF patients remains unknown. The ability of the LCI to detect treatment effects within hours after an intervention would be invaluable to the development of new therapeutic interventions for CF patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypertonic Saline | Active comparator | Drug: Hypertonic Saline 7%The treatment intervention is 1 inhalation of 7% hypertonic saline (4ml) |
| Isotonic Saline | Placebo comparator | Drug: Isotonic Saline 0.9% (Placebo)The placebo intervention is 1 inhalation of 0.9% isotonic saline |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
- Informed consent and verbal assent (as appropriate) provided by the subject's parent or legal guardian and the subject
- At least six years of age at enrolment
- Able to perform reproducible spirometry meeting American Thoracic Society standards
- Pre-bronchodilator FEV1 % predicted > or equal to 40 % predicted
Key exclusion criteria (11 listed)
- Known respiratory culture positive for Burkholderia cepacia
- Previous lung transplantation
- Use of intravenous antibiotics within 14 days of screening
- Use of oral antibiotics including prophylactic antibiotics (e.g., augmentin, tetracycline, cloxacillin, cephalosporins, septra, bactrim) within 14 days of screening
- Initiation of a new maintenance (e.g high dose ibuprofen, Pulmozyme®, aerosolized antibiotics) within 14 days of screening
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 |
|---|---|---|
| Hypertonic Saline 7%PARI Hyper-Sal™ Sodium Chloride Solution - 7% | Drug | Hypertonic Saline |
| Isotonic Saline 0.9% (Placebo) | Drug | Isotonic Saline |
Primary outcome
Lung Clearance Index
Time frame: Baseline to 24 hrs post dose
The change in the Lung Clearance Index as measured by nitrogen washout between baseline and 24 hours after each inhalation of Hypertonic Saline (7%) and Isotonic Saline (0.9%)
3 secondary outcomes
Pulmonary Function Testing
Time frame: Baseline, 1,2,4 and 24hrs post-dose
Lung Clearance Index measured using Mass Spectroscopy
Time frame: Baseline, 1,2,4 and 24 hrs post dose
Lung Clearance Index measured using Nitrogen Washout
Time frame: Baseline, 1,2, 4hrs post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2015.
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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.
Reshma Amin, MD principal investigator
The Hospital for Sick Children
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hypertonic Saline 7% in people with Cystic Fibrosis, run by The Hospital for Sick Children at 2 sites in Canada.
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 6 inclusion and 11 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: finished, as of the sponsor's last update on 22 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lung Clearance Index (time frame: Baseline to 24 hrs post dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 May 2015.