Inhaled Xylitol Versus Saline in Stable Subjects With Cystic Fibrosis

September 28, 2018 updated by: Joseph Zabner

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60614
        • Ann & Robert H. Lurie Children's Hospital of Chicago

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Aerosolized Hypertonic xyltiol
Aerosolized xylitol (5 ml) twice daily for 14 days
Drug: Xylitol
Aerosolized 15% xylitol, 5 ml twice a day for 2 weeks
Other Names:
  • Xylo-pentane-1, 2, 3, 4, 5-pentol
Drug: Hypertonic saline
4 ml of 7 % saline aerosolized twice a day for 2 weeks
Other Names:
  • 7% 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 Names:
  • Xylo-pentane-1, 2, 3, 4, 5-pentol
Drug: Hypertonic saline
4 ml of 7 % saline aerosolized twice a day for 2 weeks
Other Names:
  • 7% NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in FEV1 % Predicted From Baseline
Time Frame: Baseline and 14 days
Change from baseline in FEV1(maximal amount of air you can forcefully exhale in one second) % predicted
Baseline and 14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sputum Density
Time Frame: baseline and 14 days
Difference from baseline in density of Pseudomonas aeruginosa colonization per gram of sputum,
baseline and 14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Joseph Zabner

Collaborators

Northwestern University
Ann & Robert H Lurie Children's Hospital of Chicago

Investigators

  • Principal Investigator: Joseph Zabner, MD, University of Iowa
  • Study Director: Lakshmi Durairaj, MD, University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (ACTUAL)

February 1, 2015

Study Completion (ACTUAL)

February 1, 2015

Study Registration Dates

First Submitted

May 16, 2011

First Submitted That Met QC Criteria

May 17, 2011

First Posted (ESTIMATE)

May 18, 2011

Study Record Updates

Last Update Posted (ACTUAL)

October 24, 2018

Last Update Submitted That Met QC Criteria

September 28, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201209728

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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