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

NCT ID: NCT02276898

Last Updated: 2015-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2014-09-30

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Hypertonic Saline

The treatment intervention is 1 inhalation of 7% hypertonic saline (4ml)

Group Type: ACTIVE_COMPARATOR

Hypertonic Saline 7%

Intervention Type: DRUG

PARI Hyper-Sal™ Sodium Chloride Solution - 7%

Isotonic Saline

The placebo intervention is 1 inhalation of 0.9% isotonic saline

Group Type: PLACEBO_COMPARATOR

Isotonic Saline 0.9% (Placebo)

Intervention Type: DRUG

Interventions

Hypertonic Saline 7%

PARI Hyper-Sal™ Sodium Chloride Solution - 7%

Intervention Type: DRUG

Isotonic Saline 0.9% (Placebo)

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Reshma Amin

Staff Respirologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Reshma Amin, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

St. Michaels Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

1000024909

Identifier Type: -

Identifier Source: org_study_id