Inhaled Xylitol Versus Saline in Stable Subjects With Cystic Fibrosis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Ann & Robert H Lurie Children's Hospital of Chicago
Northwestern University
Information provided by (Responsible Party):
Joseph Zabner, University of Iowa
ClinicalTrials.gov Identifier:
NCT01355796
First received: May 16, 2011
Last updated: March 13, 2014
Last verified: March 2014

May 16, 2011
March 13, 2014
May 2011
September 2015   (final data collection date for primary outcome measure)
Safety [ Time Frame: 98 days ] [ Designated as safety issue: Yes ]
Safety as assessed by FEV1(maximal amount of air you can forcefully exhale in one second) change from baseline, adverse events and respiratory symptom score.
Safety [ Time Frame: 98 days ] [ Designated as safety issue: Yes ]
Safety as assessed by FEV1 change from baseline, adverse events and respiratory symptom score.
Complete list of historical versions of study NCT01355796 on ClinicalTrials.gov Archive Site
Efficacy [ Time Frame: 98 days ] [ Designated as safety issue: No ]
Efficacy include density of colonization per gram of sputum, time to next exacerbation , sputum cytokines and revised CF quality of life questionnaire.
Same as current
Not Provided
Not Provided
 
Inhaled Xylitol Versus Saline in Stable Subjects With Cystic Fibrosis
Randomized Cross Over Study of Inhaled Hypertonic Xylitol Versus Hypertonic Saline in Stable Subjects With 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 plan to study the safety and efficacy of 2 weeks of inhaled xylitol compared to 2 weeks of hypertonic saline in a randomized crossover design in stable subjects with cystic fibrosis

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. The investigators 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, the investigators observed that single doses of 10% followed by 15% xylitol was well tolerated by subjects with cystic fibrosis who were stable.

In this study, the investigators plan to study the safety and efficacy of 2 weeks of inhaled xylitol compared to 2 weeks of hypertonic saline in a randomized crossover design in stable subjects with cystic fibrosis

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Cystic Fibrosis
  • Drug: Xylitol
    Aerosolized 15% xylitol, 5 ml twice a day for 2 weeks
    Other Name: Xylo-pentane-1, 2, 3, 4, 5-pentol
  • Drug: Xylo-pentane-1,2,3,4 5-pentol
    5 ml of 15 % aerosolized 2 times per day
    Other Name: NaCl
  • Experimental: Aerosolized Hypertonic xyltiol

    Drug

    Aerosolized xylitol (5 ml) twice daily for 14 days

    Interventions:
    • Drug: Xylitol
    • Drug: Xylo-pentane-1,2,3,4 5-pentol
  • Active Comparator: Hypertonic saline
    Aerosolized 7% hypertonic saline (4 ml) twice daily for 14 days
    Interventions:
    • Drug: Xylitol
    • Drug: Xylo-pentane-1,2,3,4 5-pentol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
30
December 2015
September 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Documented diagnosis of CF (medical record evidence of 2 identified CFTR(Cystic fibrosis transmembrane conductance regulator) mutations or a positive sweat chloride test or nasal voltage difference, and 1 or more clinical findings of CF)
  • Age 16 or greater
  • FEV1>30% predicted
  • Oxygen saturation > or equal too 90% on room air
  • Clinically stable, without evidence of pulmona4ry exacerbation for at least 2 weeks prior to screening (defined as use of oral or intravenous antibiotics for cystic fibrosis exacerbation)
  • Use of effective contraception in women
  • Ability to provide written informed consent and assent
  • Successful completion of the trial doses of study drugs

Exclusion Criteria:

  • Pregnancy
  • Hemoptysis more than 100 mL within the last 30 days
  • Change in chronic medication within the last 30 days
  • History of elevated serum creatinine (> than or equal to 2 mg/dl) within 30 days or at screening
  • History of lung and other solid organ transplantation
  • Wait-listed for lung or other solid organ transplant
  • Known intolerance to inhaled hypertonic saline
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01355796
UO1 HL102288
Yes
Joseph Zabner, University of Iowa
University of Iowa
  • Ann & Robert H Lurie Children's Hospital of Chicago
  • Northwestern University
Principal Investigator: Joseph Zabner, MD University of Iowa
Study Director: Lakshmi Durairaj, MD University of Iowa
University of Iowa
March 2014

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