Aerosolized Hypertonic Xylitol Versus Hypertonic Saline in Cystic Fibrosis (CF) Subjects

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Iowa
Sponsor:
Information provided by (Responsible Party):
Joseph Zabner, University of Iowa
ClinicalTrials.gov Identifier:
NCT00928135
First received: June 18, 2009
Last updated: March 13, 2014
Last verified: March 2014

June 18, 2009
March 13, 2014
June 2009
July 2014   (final data collection date for primary outcome measure)
The primary outcomes will be safety as assessed by FEV1 change from baseline, adverse events and respiratory symptom score. [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00928135 on ClinicalTrials.gov Archive Site
Outcomes for trend in efficacy include density of colonization per gram of sputum, time to next exacerbation, sputum cytokines and revised CF quality of life questionnaire. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Aerosolized Hypertonic Xylitol Versus Hypertonic Saline in Cystic Fibrosis (CF) Subjects
Randomized Controlled Study of Aerosolized Hypertonic Xylitol Versus Hypertonic Saline in Hospitalized Patients With Exacerbation of Cystic Fibrosis

Cystic fibrosis (CF) lung disease is characterized by chronic bacterial colonization and recurrent infection of the airways. Lowering the airway surface liquid (ASL) salt concentration has been shown to increase activity of salt sensitive antimicrobial peptides.

Xylitol is a 5-carbon sugar that can lower the ASL salt concentration, thus enhancing innate immunity. In this study, the investigators propose to test the safety and tolerability of aerosolized xylitol used daily for 2 weeks in subjects with cystic fibrosis. In a pilot, 2-week study, 60 subjects with cystic fibrosis with an FEV1(Forced expiratory volume in 1 second ) >30% predicted will be randomized to receive aerosolized 7% hypertonic saline (5 ml) or 15% xylitol, (5 ml) twice a day for 14 days. The primary outcomes will be safety as assessed by FEV1 change from baseline, adverse events and respiratory symptom score. Outcomes for trend in efficacy include density of colonization of sputum, time to next exacerbation, sputum cytokines and revised CF quality of life questionnaire.

Cystic fibrosis (CF) lung disease is characterized by chronic bacterial colonization and recurrent infection of the airways. Disruption of the cystic fibrosis transmembrane conductance regulator chloride channels in subjects with CF results in altered fluid and electrolyte transport across the airway epithelium thereby initiating infections.

These infections eventually destroy the lungs and contribute to significant morbidity and mortality in patients with CF. It is well known that antibacterial activity of innate immune mediators such as lysozyme and beta defensins in human airway surface liquid (ASL) is salt-sensitive; an increase in salt concentration inhibits their activity.

Conversely, their activity is increased by low ionic strength. Lowering the ASL salt concentration and increasing the ASL volume might therefore potentiate innate immunity and therefore decrease or prevent airway infections in subjects with CF.

Xylitol, a five-carbon sugar with low transepithelial permeability, which is poorly metabolized by bacteria can lower the salt concentration of both cystic fibrosis (CF) and non-CF epithelia in vitro. Xylitol is an artificial sweetener that has been successfully used in chewing gums to prevent dental caries; it has been used as an oral sugar substitute without significant adverse effects. It has also been shown to decrease the incidence of acute otitis media by 20-40%; nasal application to normal human subjects was found to decrease colonization with coagulase negative staphylococcus. We found that aerosolized iso-osmolar xylitol was safe in mice, healthy volunteers and stable subjects with CF when administered over a single day. In a recent study, we observed that single doses of 10% followed by 15% xylitol was well tolerated by subjects with cystic fibrosis who were stable. In this pilot study we propose to test the hypothesis that aerosolized hypertonic xylitol given daily for 2 weeks, will be safe and well tolerated and potentially lower the density of colonization in subjects with CF compared to hypertonic saline. We chose hypertonic concentration of xylitol to be comparable in part to hypertonic saline which is being offered as a routine treatment in hospitalized patients with CF exacerbation.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Cystic Fibrosis
  • Drug: Xylitol
    15% xylitol solution for aerosol; Dosage: 5 ml twice a day (BID)
  • Drug: Saline
    7% hypertonic saline solution for aerosol; Dosage: 5 ml twice a day (BID)
  • Active Comparator: 7% Hypertonic saline
    5 ml of 7% saline twice daily
    Intervention: Drug: Saline
  • Experimental: Hypertonic xylitol
    5 ml of 15% xylitol twice daily
    Intervention: Drug: Xylitol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
October 2014
July 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subjects with CF (medical record evidence of CFTR(Cystic fibrosis transmembrane conductance regulator) mutation or sweat chloride test or nasal voltage difference, and 1 or more clinical findings of CF),
  • Age 12 or greater
  • FEV1 > 30% predicted(within the last 14 days and oxygen saturation > 90% on FiO2(fraction of inspired oxygen) ≤ 50%,
  • Admitted for an exacerbation,
  • Use of effective contraception in women,
  • Able to provide written informed consent.

Exclusion Criteria:

  • Pregnancy,
  • History of asthma based on methacholine challenge or bronchial hyperresponsiveness on PFTS(Pulmonary Function Test),
  • Hemoptysis more than 60 mL within the last 30 days,
  • Use of any investigational study drug within the last 30 days,
  • Initiation of hypertonic saline within the last 30 days,
  • A serum creatinine 2 mg/dl or more
  • Active malignancy in the last year
  • Antibiotics for CF exacerbation as an outpatient in the last 2 weeks
  • B cepacia colonization
  • Waiting list for lung transplant
  • Lack of FEV1 data from the last 14 days
  • Previous participation in this study
Both
12 Years and older
No
Contact: Jan L Launspach, R.N., CCRC (319)356-2047 janice-launspach@uiowa.edu
United States
 
NCT00928135
Xylitol, IND 66,427
Yes
Joseph Zabner, University of Iowa
University of Iowa
Not Provided
Principal Investigator: Joseph Zabner, M.D. PMID: 16781897
Study Director: Lakshmi Durairaj, M.D. PMID: 16781897
Study Chair: Jan L Launspach, R.N., CCRC PMID: 16781897
University of Iowa
March 2014

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