Effect of Hypertonic Saline on Mucus Clearance in Children Ages 5-12 With Cystic Fibrosis

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Scott Donaldson, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01031706
First received: December 11, 2009
Last updated: May 29, 2014
Last verified: March 2014
  Purpose

Previous work demonstrated that inhaled hypertonic saline (HS) reduces exacerbation frequency and improves lung function in adults with cystic fibrosis (CF). It is unclear, however, whether HS will benefit young patients suffering from CF. The investigators propose to further support the concept that HS can benefit children with mild CF lung disease by performing a relatively short, placebo controlled study of HS in 5-12 year olds, using lung function and mucociliary clearance as key outcome measures.


Condition Intervention
Cystic Fibrosis
Drug: Hypertonic Saline
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Sustained Impact of Hypertonic Saline on Mucociliary Clearance in Young Children With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Change in Mucociliary Clearance Rate [ Time Frame: Baseline versus after completion of 4 week treatment period ] [ Designated as safety issue: No ]

    Average radio tracer clearance through 90 minutes (MCC90) is primary index of mucociliary clearance at each study.

    Primary study outcome: is absolute change in MCC90 between baseline and at end of treatment (where MCC measured 8-12 hours after final dose of study drug) - reflects sustained impact on MCC



Secondary Outcome Measures:
  • FEV1 (Spirometry) Change [ Time Frame: Baseline and after 4 weeks of treatment ] [ Designated as safety issue: Yes ]
    Absolute change in % predicted FEV1 between baseline and after 4 weeks of treatment calculated


Enrollment: 23
Study Start Date: September 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypertonic saline
6% NaCl, 4 ml TID via eFlow
Drug: Hypertonic Saline
inhaled HS (6% NaCl, 4mL) three times a day for 28 days
Other Name: HS
Placebo Comparator: Placebo
0.12% x 4ml via eFlow nebulizer
Drug: Placebo
4 ml 0.12% NaCl inhaled three times a day x 28 days

Detailed Description:

Our current understanding of the pathogenesis of CF lung disease stems from data that demonstrate the presence of airway surface liquid (ASL) dehydration in CF. ASL dehydration in CF is caused by defective chloride secretion through the cystic fibrosis transmembrane regulator (CFTR) and increased sodium reabsorption through the epithelial sodium channel (ENaC). ASL dehydration, in turn, interferes with the mucociliary clearance apparatus, causing a breach in a critical line of lung host defense. A number of novel therapeutics are now being developed to address this basic defect of disease, including the use of inhaled hypertonic saline.

Previous work demonstrated that inhaled hypertonic saline (HS) reduces exacerbation frequency and improves lung function in patients with clinically apparent lung disease. A number of issues revolving around the use of HS in CF remain unresolved. First, the typical patients enrolled in previous studies were adults (mean age = 26 yrs) with established lung disease (mean FEV1=78%). Despite our hypothesis that HS should positively affect MCC in preserved/normal airways, a common view of HS is that it benefits CF patients by inducing cough and transiently promoting the clearance of thick CF secretions. It has been questioned, therefore, whether HS will benefit patients who are younger and have mild (or undetectable) lung disease and potentially normal (though unmeasured) rates of MCC. Second, it is unclear whether the substantial beneficial effects of HS in CF were achieved because of a long (>4 hours) duration of action or in spite of an extremely short (~45 minutes) duration of action (the traditional view based upon experiments in normal epithelia). This issue is important, as it relates to the development and dosing of hydrator therapies that may have different pharmacodynamic profiles. Certainly, if twice daily dosing of a short acting compound is sufficient to provide significant clinical benefit, it would reduce the challenge of drug discovery for CF and ease the treatment burden imposed upon patients. The study of HS in CF provides us an opportunity to address this issue.

The hypothesis being tested is that HS will rehydrate CF airway secretions, producing a sustained acceleration in MCC in young children with CF, regardless of whether a measurable mucus clearance defect exists at this relatively early stage of disease. We predict a substantial acceleration of MCC will reduce the exacerbation rate in young children with CF. In addition, with the growing number of treatment modalities that are prescribed to patients with CF, adherence to complex and time consuming medical regimens becomes increasingly problematic and important. We therefore, wish to test an improved drug delivery platform for HS- the eFlow (Pari Pharma) vibrating mesh nebulizer, which has the potential to reduce treatment times, improve compliance, and increase treatment efficacy.

  Eligibility

Ages Eligible for Study:   5 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Gender: Females or Males. If the subject is female and of childbearing potential (first menses has occurred), she must have a documented negative pregnancy test at screening and prior to each mucociliary clearance study. Those of childbearing potential must be abstinent or using an acceptable method of birth control (i.e. an Intrauterine Contraceptive Device with a failure rate of <1%, hormonal contraceptives or a barrier method).
  • Age: 5-12 years, inclusive
  • Diagnosis: Cystic fibrosis documented by a compatible clinical presentation and sweat chloride > 60 mEq/l or 2 disease causing CFTR mutations.
  • Severity of the Disease: Suitable patients will have mild lung disease, as defined by:

    • Pulmonary Function: Each patient must have an FEV1 of greater than or equal to 60% of predicted at the screening visit.
    • Hemoglobin saturation: Patients must have an oxygen saturation of >92% on room air as determined by pulse oximetry at the screening visit.
  • Informed consent - The patient and a parent or legally authorized guardian must agree to the subject's participation in the study by signing and dating the informed consent/assent forms after the nature of the study has been fully explained and all questions have been satisfactorily answered.

Exclusion Criteria:

  • Unstable or asthmatic lung disease: As defined by a change in medical regimen during the preceding 2 weeks; an FEV1 15% below recent (within 6 months) clinical measurements. Patients with a history of co-existent asthma, as manifested by wheezing and significant bronchoreactivity (>15% increase in FEV1 with bronchodilator), will also be excluded.
  • Other medication usage: Patients unable or unwilling to be withdrawn from hypertonic saline therapy for two weeks prior to Visit 1 (baseline MCC visit). Patients using Pulmozyme will be permitted to participate in this trial. Patients on chronic, cycling antibiotics will be required to have completed at least 2 full cycles of the prescribed antibiotic prior to enrollment and should not cycle on or off this therapy during the treatment period of the study.
  • Spirometry Performance: Those subjects who are unable to perform acceptable, reproducible spirometry will be excluded from this study.
  • Drug allergy: A history of allergy or intolerance to any of the study medications, including albuterol or hypertonic saline.
  • Have received an investigational drug or therapy during the preceding 30 days.
  • Have had radiation exposure within the past year that would cause them to exceed Federal Regulations by participating in this study.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01031706

Locations
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Scott H Donaldson, MD University of North Carolina, Chapel Hill
  More Information

Publications:
Responsible Party: Scott Donaldson, MD, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01031706     History of Changes
Other Study ID Numbers: 09-1258, 1P50HL084934
Study First Received: December 11, 2009
Results First Received: March 5, 2014
Last Updated: May 29, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by University of North Carolina, Chapel Hill:
Hypertonic Saline
Pediatrics
Cystic Fibrosis
Mucociliary Clearance
Lung Clearance Index

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 20, 2014