Effect of Hypertonic Saline on Mucus Clearance in Children Ages 5-12 With Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Hypertonic Saline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): inhaled HS (6% NaCl, 4mL) three times a day for 28 days; 4 ml 0.12% NaCl inhaled three times a day x 28 days
Other intervention name(s): HS; .12% NaCl
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hypertonic Saline; Pediatrics; Cystic Fibrosis; Mucociliary Clearance; Lung Clearance Index