A Randomized-Controlled Trial of Inhaled Hypertonic Saline (7%) to Evaluate the Lung Clearance Index
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02276898|
Recruitment Status : Completed
First Posted : October 28, 2014
Last Update Posted : May 22, 2015
|Condition or disease||Intervention/treatment||Phase|
|Cystic Fibrosis||Drug: Hypertonic Saline 7% Drug: Isotonic Saline 0.9% (Placebo)||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|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.|
|Study Start Date :||November 2011|
|Actual Primary Completion Date :||September 2014|
|Actual Study Completion Date :||September 2014|
Active Comparator: Hypertonic Saline
The treatment intervention is 1 inhalation of 7% hypertonic saline (4ml)
Drug: Hypertonic Saline 7%
PARI Hyper-Sal™ Sodium Chloride Solution - 7%
Placebo Comparator: Isotonic Saline
The placebo intervention is 1 inhalation of 0.9% isotonic saline
Drug: Isotonic Saline 0.9% (Placebo)
- 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%)
- Pulmonary Function Testing [ Time Frame: Baseline, 1,2,4 and 24hrs post-dose ]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.
- Lung Clearance Index measured using Mass Spectroscopy [ Time Frame: Baseline, 1,2,4 and 24 hrs post dose ]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.
- Lung Clearance Index measured using Nitrogen Washout [ Time Frame: Baseline, 1,2, 4hrs post dose ]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%)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02276898
|The Hospital for Sick Children|
|Toronto, Ontario, Canada, M5V1X8|
|St. Michaels Hospital|
|Toronto, Ontario, Canada|
|Principal Investigator:||Reshma Amin, MD||The Hospital for Sick Children|