The Effect of Hypertonic Saline on the Lung Clearance Index in Patients With Cystic Fibrosis

Sponsor

The Hospital for Sick Children (Other)

Overall Status

Completed

CT.gov ID

NCT00635141

Collaborator

Canadian Cystic Fibrosis Foundation (Other)

Enrollment

Location

Arms

Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is examining the effect of hypertonic saline compared to placebo on the Lung Clearance Index in Cystic Fibrosis patients.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: hypertonic saline (7 %) and isotonic saline (0.9%) Drug: hypertonic saline (7 %) and isotonic saline (0.9%)	Phase 3

Detailed Description

The life expectancy of patients with Cystic Fibrosis (CF) has greatly increased over time due to improved clinical care. While this is certainly beneficial to CF patients, the overall stability in lung function has made it more difficult to assess the effect of therapeutic interventions. Currently, FEV1 (forced expiratory volume in 1 second) remains the primary outcome measure for most clinical trials, but many CF patients have normal pulmonary function and the annual rate of decline is now less than 2% in large specialized centres. Therefore, additional parameters are needed that are more sensitive parameters to define abnormalities in CF patients and be used in therapeutic trials.

One such promising parameter is the Lung Clearance Index (LCI). The LCI is a test to quantify ventilation inhomogeneity by assessing the washout of an inhaled inert gas. Abnormalities in gas clearance from the lung are largely due to retention of inhaled gases due to mucous obstruction in the lower airways.

Interventions that improve mucus accumulation are expected to improve the LCI. Hypertonic saline has been shown to increase airway surface liquid (ASL), mucociliary clearance and pulmonary function. Therefore, this study will examine the effect of hypertonic saline compared to placebo on the Lung Clearance Index in Cystic Fibrosis patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

The Effect of Inhaled Hypertonic Saline (7%) Versus Normal Saline (0.9%) on the Lung Clearance Index in Patients With Cystic Fibrosis

Study Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: hypertonic saline (7 %) and isotonic saline (0.9%) Patients in study arm 1 will receive hypertonic saline (7 %) during the first phase of the study and will crossover to placebo (0.9% isotonic saline) during the second phase. Both drugs will be administered via PARI LC® Star reusable nebulizer.
Experimental: 2	Drug: hypertonic saline (7 %) and isotonic saline (0.9%) Patients in study arm 2 will receive placebo (0.9% isotonic saline) during the first phase of the study and will crossover to hypertonic saline (7 %) during the second phase. Both drugs will be administered via PARI LC® Star reusable nebulizer.

Arm

Intervention/Treatment

Experimental: 1

Drug: hypertonic saline (7 %) and isotonic saline (0.9%)

Patients in study arm 1 will receive hypertonic saline (7 %) during the first phase of the study and will crossover to placebo (0.9% isotonic saline) during the second phase. Both drugs will be administered via PARI LC® Star reusable nebulizer.

Experimental: 2

Drug: hypertonic saline (7 %) and isotonic saline (0.9%)

Patients in study arm 2 will receive placebo (0.9% isotonic saline) during the first phase of the study and will crossover to hypertonic saline (7 %) during the second phase. Both drugs will be administered via PARI LC® Star reusable nebulizer.

Outcome Measures

Primary Outcome Measures

Change in LCI from baseline to end of treatment in hypertonic saline treated patients versus patients receiving placebo (isotonic saline) [Duration of patient's involvement in study]

Secondary Outcome Measures

Change in FEV1 % predicted [Duration of patient's involvement in study]
Change in FVC (forced vital capacity) % predicted [Duration of patient's involvement in study]
Change in FEF25-75% (forced expiratory flow between 25 and 75 % of vital capacity) predicted [Duration of patient's involvement in study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 18 Years

Sexes Eligible for Study:

All

Accepts 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
6-18 years of age at enrolment and able to perform reproducible spirometry
Clinically stable at enrolment
FEV1 % predicted ≥ 80 % as calculated by the Wang reference equations
Ability to comply with medication use, study visits and study procedures

Exclusion Criteria:

Respiratory culture positive for NTM or B. cepacia complex within past year or screening
Use of intravenous antibiotics or oral quinolones within 14 days of screening
Investigational drug use within 30 days of screening
Physical findings at screening that would compromise the safety of the participant or the quality of the study data