Inhaled Xylitol Versus Saline 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

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