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

Primary Purpose

Cystic Fibrosis

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Hypertonic Saline 7%

Isotonic Saline 0.9% (Placebo)

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring pediatric, lung clearance index, Multiple Breath Washout, Hypertonic Saline

Eligibility Criteria

6 Years - 18 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

The Hospital for Sick Children
St. Michaels Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Hypertonic Saline

Isotonic Saline

Arm Description

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

The placebo intervention is 1 inhalation of 0.9% isotonic saline

Outcomes

Primary Outcome Measures

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%)

Secondary Outcome Measures

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.

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.

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%)

Full Information

NCT ID

NCT02276898

First Posted

October 22, 2014

Last Updated

May 20, 2015

Sponsor

The Hospital for Sick Children

1. Study Identification

Unique Protocol Identification Number

NCT02276898

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

May 2015

Overall Recruitment Status

Completed

Study Start Date

November 2011 (undefined)

Primary Completion Date

September 2014 (Actual)

Study Completion Date

September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The Hospital for Sick Children

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

Keywords

pediatric, lung clearance index, Multiple Breath Washout, Hypertonic Saline

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Hypertonic Saline

Arm Type

Active Comparator

Arm Description

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

Arm Title

Isotonic Saline

Arm Type

Placebo Comparator

Arm Description

The placebo intervention is 1 inhalation of 0.9% isotonic saline

Intervention Type

Drug

Intervention Name(s)

Hypertonic Saline 7%

Intervention Description

PARI Hyper-Sal™ Sodium Chloride Solution - 7%

Intervention Type

Drug

Intervention Name(s)

Isotonic Saline 0.9% (Placebo)

Primary Outcome Measure Information:

Title

Lung Clearance Index

Description

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%)

Time Frame

Baseline to 24 hrs post dose

Secondary Outcome Measure Information:

Title

Pulmonary Function Testing

Description

Time Frame

Baseline, 1,2,4 and 24hrs post-dose

Title

Lung Clearance Index measured using Mass Spectroscopy

Description

Time Frame

Baseline, 1,2,4 and 24 hrs post dose

Title

Lung Clearance Index measured using Nitrogen Washout

Description

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%)

Time Frame

Baseline, 1,2, 4hrs post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Reshma Amin, MD

Organizational Affiliation

The Hospital for Sick Children

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Hospital for Sick Children

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5V1X8

Country

Canada

Facility Name

St. Michaels Hospital

City

Toronto

State/Province

Ontario

Country

Canada

12. IPD Sharing Statement

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

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