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A Randomized-Controlled Trial of Inhaled Hypertonic Saline (7%) to Evaluate the Lung Clearance Index

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ClinicalTrials.gov Identifier: NCT02276898
Recruitment Status : Completed
First Posted : October 28, 2014
Last Update Posted : May 22, 2015
Sponsor:
Information provided by (Responsible Party):
Reshma Amin, The Hospital for Sick Children

Brief 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. As such, determining if it can be used as a short term pharmacodynamic biomarker is paramount.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Hypertonic Saline 7% Drug: Isotonic Saline 0.9% (Placebo) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
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)



Primary Outcome Measures :
  1. 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%)


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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%)



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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

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


Locations
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Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5V1X8
St. Michaels Hospital
Toronto, Ontario, Canada
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
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Principal Investigator: Reshma Amin, MD The Hospital for Sick Children
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Responsible Party: Reshma Amin, Staff Respirologist, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT02276898    
Other Study ID Numbers: 1000024909
First Posted: October 28, 2014    Key Record Dates
Last Update Posted: May 22, 2015
Last Verified: May 2015
Keywords provided by Reshma Amin, The Hospital for Sick Children:
pediatric
lung clearance index
Multiple Breath Washout
Hypertonic Saline
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases