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

The Hospital for Sick Children

Status and phase

Completed

Phase 2

Conditions

Cystic Fibrosis

Treatments

Drug: Isotonic Saline 0.9% (Placebo)

Drug: Hypertonic Saline 7%

Study type

Interventional

Funder types

Other

Identifiers

NCT02276898

1000024909

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 estimated patients

Sex

All

Ages

6 to 18 years old

Volunteers

No Healthy Volunteers

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