Hypertonic Saline and Mucociliary Clearance in Children

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by:
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01293084
First received: February 9, 2011
Last updated: NA
Last verified: January 2011
History: No changes posted

February 9, 2011
February 9, 2011
July 2007
June 2009   (final data collection date for primary outcome measure)
Percent mucociliary clearance at 60 minutes [ Time Frame: 60 minutes ] [ Designated as safety issue: No ]
Same as current
No Changes Posted
Percent mucociliary clearance at 90 minutes [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Hypertonic Saline and Mucociliary Clearance in Children
Acute Inhalation of Hypertonic Saline Does Not Improve Mucociliary Clearance in All Children With Cystic Fibrosis

Previously, the investigators and others have shown that mucociliary clearance (MCC) is defective in patients with cystic fibrosis (CF) and it is now thought that alterations in airway mucus rheology figure prominently in the impairment. Mucociliary clearance works by trapping toxic particles, bacteria and viruses in the lung mucus and then quickly removing the mucus out of the lungs. Defects in MCC typically lead to the accumulation of mucus in the airways, and this in turn is associated with acute infections, chronic bacterial colonization and chronic inflammation. One treatment strategy that is gaining acceptance as an important therapy for improving MCC in adults with CF is the inhalation of the osmotic stimulus, hypertonic saline (HS). A number of studies have shown that acute inhalation of HS (7% saline) significantly improves MCC in adults with CF and results from a recent study indicate that two weeks of inhaling HS leads to a significant increase in MCC that is sustained for 8 hours post inhalation and is associated with significant improvements in FEV1, FVC and FEF25-75 values. Since MCC in patients with CF appears to be impaired by adulthood, any drug that disrupts or slows the impairment in childhood could prove enormously beneficial in the long-term prognosis of the disease. Nevertheless, no studies have been conducted to determine if HS treatment improves MCC in children with CF. This is most problematic for physicians who care for children with CF who have normal FEV1 and FVC values, since it is unclear if they should treat these children with HS or not. This research study is designed to begin to answer this question. The investigators hypothesize that acute inhalation of hypertonic saline (7%) will improve MCC in CF children with normal pulmonary function. Our hypothesis will be tested in a one-year clinical trial that will be randomized and placebo-controlled. Twelve children with CF who are 7-12 years old and have normal FEV1 and FVC values will participate. Our goal will be to compare MCC in these children on two study visits after acute inhalations of placebo (0.12% saline) or hypertonic saline (HS) (7% saline) aerosol. The investigators predict that MCC values after acute inhalation of 7% HS aerosol will be statistically significantly greater than after placebo inhalation.

Several studies report that mucociliary clearance (MCC) is impaired in adults with CF. Because MCC is an important airway defense mechanism, drugs that slow impairment of MCC in children could prove beneficial in the long-term prognosis of the disease. A few studies have shown that inhalation of hypertonic saline (HS) significantly improves MCC in adults with CF and improvement is associated with increases in pulmonary function and decreases in pulmonary exacerbations. Nevertheless, no studies have examined if HS improves MCC in CF children. This is problematic for physicians who care for CF children with normal pulmonary function, since it is unclear if they should treat with HS or not. This study was designed to begin to answer this question. Twelve children with CF (7-12 yrs; 5 males) and normal pulmonary function (FEV1 and FVC > 90% of predicted values) participated in a screening visit and two study visits. On the screening visit, children underwent an induced sputum test. On the two study visits, they inhaled 0.12% saline (placebo), or HS, in a double-blind, randomized, cross-over study. Following inhalation of placebo or HS, patients inhaled the radioisotope 99mtechnetium and underwent sequential imaging of their lungs with a gamma camera for 90 min and approximately 24 hrs later. Mucociliary clearance was quantified at 60 min (MCC60), 90 min (MCC90) and 24 hrs (MCC24hrs) after inhalation of the radioisotope. Between the 60 min and 90 min measurements, children coughed 30 times.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Cystic Fibrosis
  • Drug: 0.12% saline
    5mL of 0.12% saline inhaled once over 20 minutes
  • Drug: 7% saline
    5mL 7% saline inhaled once over 20 minutes
    Other Name: hypertonic saline
  • Experimental: 7% saline
    5 mL of 7% saline was inhaled once over a 20 minute period.
    Intervention: Drug: 7% saline
  • Placebo Comparator: 0.12% saline
    5mL 0.12% saline inhaled once during 20 minutes
    Intervention: Drug: 0.12% saline
Laube BL, Sharpless G, Carson KA, Kelly A, Mogayzel PJ Jr. Acute inhalation of hypertonic saline does not improve mucociliary clearance in all children with cystic fibrosis. BMC Pulm Med. 2011 Sep 6;11:45. doi: 10.1186/1471-2466-11-45.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
June 2009
June 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Males and females
  • Age 7-12 years old
  • Diagnosis of cystic fibrosis by sweat chloride > 60 meq/L, or presence of two CFTR mutations known to cause CF
  • Routinely treated with the short-acting bronchodilator albuterol
  • FEV1 > 90% of predicted values

Exclusion Criteria:

  • FEV1 < 90% of predicted values
  • Routine use of hypertonic saline, mannitol, or amiloride
  • Allergic bronchopulmonary aspergillosis (ABPA)
  • Sputum colonization with Burkholderia cepacia or multiple antibiotic resistant organisms
  • Evidence of a pulmonary exacerbation within past two weeks
  • Treated with intravenous or oral antibiotics in the past two weeks for a pulmonary exacerbation
  • Presence of an acute respiratory illness characterized by:

    • Coughing above baseline values
    • Wheezing
    • Respiratory distress
    • Hemoptysis
  • Cannot perform the inhalation maneuvers that are required for drug inhalation or radioaerosol administration
Both
7 Years to 12 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01293084
CFF Account #LAUBE06A0
No
Beth Laube/Professor, Johns Hopkins University School of Medicine
Johns Hopkins University
Cystic Fibrosis Foundation
Principal Investigator: Beth L Laube, PhD Johns Hopkins University
Johns Hopkins University
January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP