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
  Purpose

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


Condition Intervention Phase
Cystic Fibrosis
Drug: Xylitol
Drug: Xylo-pentane-1,2,3,4 5-pentol
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Cross Over Study of Inhaled Hypertonic Xylitol Versus Hypertonic Saline in Stable Subjects With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 30
Study Start Date: May 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aerosolized Hypertonic xyltiol

Drug

Aerosolized xylitol (5 ml) twice daily for 14 days

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
Active Comparator: Hypertonic saline
Aerosolized 7% hypertonic saline (4 ml) twice daily for 14 days
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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01355796

Locations
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60614
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
University of Iowa
Ann & Robert H Lurie Children's Hospital of Chicago
Northwestern University
Investigators
Principal Investigator: Joseph Zabner, MD University of Iowa
Study Director: Lakshmi Durairaj, MD University of Iowa
  More Information

Publications:

Responsible Party: Joseph Zabner, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT01355796     History of Changes
Other Study ID Numbers: UO1 HL102288
Study First Received: May 16, 2011
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration

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 23, 2014