Aerosolized Hypertonic Xylitol Versus Hypertonic Saline in Cystic Fibrosis (CF) Subjects
| Status: | Completed |
|---|---|
| Conditions: | Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 12 - Any |
| Updated: | 4/17/2018 |
| Start Date: | January 22, 2013 |
| End Date: | April 9, 2018 |
Randomized Controlled Study of Aerosolized Hypertonic Xylitol Versus Hypertonic Saline in Hospitalized Patients With Exacerbation of 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 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.
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.
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.
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.
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
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