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
  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 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.


Condition Intervention Phase
Cystic Fibrosis
Drug: Xylitol
Drug: Saline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: Randomized Controlled Study of Aerosolized Hypertonic Xylitol Versus Hypertonic Saline in Hospitalized Patients With Exacerbation of Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 60
Study Start Date: June 2009
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 7% Hypertonic saline
5 ml of 7% saline twice daily
Drug: Saline
7% hypertonic saline solution for aerosol; Dosage: 5 ml twice a day (BID)
Experimental: Hypertonic xylitol
5 ml of 15% xylitol twice daily
Drug: Xylitol
15% xylitol solution for aerosol; Dosage: 5 ml twice a day (BID)

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. 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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00928135

Contacts
Contact: Jan L Launspach, R.N., CCRC (319)356-2047 janice-launspach@uiowa.edu

Locations
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Jan L Launspach, R.N., CCRC    319-356-2047    janice-launspach@uiowa.edu   
Contact: Lakshmi Durairaj, M.D.    (319) 353-7968    durairaj-lakshmi@uiowa.edu   
Principal Investigator: Joseph Zabner, M.D.         
Sub-Investigator: Lakshmi Durairaj, M.D.         
Sponsors and Collaborators
University of Iowa
Investigators
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
  More Information

Publications:
Responsible Party: Joseph Zabner, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT00928135     History of Changes
Other Study ID Numbers: Xylitol, IND 66,427
Study First Received: June 18, 2009
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on September 18, 2014