Inhaled Xylitol Versus Saline in Stable Subjects With Cystic Fibrosis
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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 |
- Safety [ Time Frame: 98 days ] [ Designated as safety issue: Yes ]Safety as assessed by FEV1 change from baseline, adverse events and respiratory symptom score.
- 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: | October 2013 |
| Estimated Primary Completion Date: | October 2013 (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 |
Inclusion Criteria:
- Documented diagnosis of CF (medical record evidence of 2 identified CFTR 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| United States, Illinois | |
| Children's Memorial Hospital | Recruiting |
| Chicago, Illinois, United States, 60614 | |
| Contact: Amy Lobner, MPH, CCRC 312-227-6858 alobner@luriechildrens.org | |
| Contact: Susanna A McColley, MD 312-227-6260 smccolle@luriechildrens.org | |
| Sub-Investigator: Susanna McColley, MD | |
| Northwestern University | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Contact: Donna Harkal, BA, BSN, RN, BC, CCRC 312-503-2160 d-harakal@northwestern.edu | |
| Contact: Manu Jain, MD, PhD 312-503-4242 m-jain@northwestern.edu | |
| Sub-Investigator: Manu Jain, MD | |
| 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: | June 12, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Cystic Fibrosis Fibrosis Pancreatic Diseases Digestive System Diseases Lung Diseases |
Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Pathologic Processes |
ClinicalTrials.gov processed this record on June 13, 2013