Cystic FibrosisPhase 1/2NCT00928135
Aerosolized Hypertonic Xylitol Versus Hypertonic Saline in Cystic Fibrosis (CF) Subjects
A Phase 1/2 study testing Xylitol and Hypertonic saline in people with Cystic Fibrosis, run by Joseph Zabner at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Xylitol and Hypertonic saline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jan 2013to 9 Apr 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
About this study
Official title: 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.
Read the 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.
- Conditions
- Cystic Fibrosis
- Being tested
- Xylitol, Hypertonic saline
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XylitolDrug
15% xylitol solution for aerosol; Dosage: 5 ml twice a day (BID)
Hypertonic salineDrug
7% hypertonic saline solution for aerosol; Dosage: 5 ml twice a day (BID)
| Study group | Role | What they receive |
|---|---|---|
| 7% Hypertonic saline | Active comparator | 5 ml of 7% saline twice daily Receives: Drug: Hypertonic saline |
| Hypertonic xylitol | Experimental | 5 ml of 15% xylitol twice daily Receives: Drug: Xylitol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in FEV1 Percentage Predicted From Baseline
Change in lung function (forced expiratory volume in 1 second) between baseline and Day 14
Measured: 14 days
Secondary outcomes (2)
Density of Colonization of Pseudomonas Aeruginosa Per Gram of Sputum
Mean difference from baseline of Sputum density expressed as log colony forming units between baseline and Day 14
Measured: 14 days
Exacerbations During 6 Months Follow-up
numbers of subjects that experienced an exacerbation during the 6 months follow-up
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2009 (estimated)
- Study start22 Jan 2013
- Primary completion9 Apr 2018
- Study completion9 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph Zabner
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Joseph Zabner, University of Iowa
- Investigators
- Joseph Zabner, M.D., Principal investigator, PMID: 16781897Lakshmi Durairaj, M.D., Study director, PMID: 16781897Jan L Launspach, R.N., CCRC, Study chair, PMID: 16781897
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00928135
- Sponsor's protocol ID
- 200901713
- Status last verified
- Oct 2020
- First submitted
- 18 Jun 2009
- Last updated
- 25 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Durairaj L, Launspach J, Watt JL, Mohamad Z, Kline J, Zabner J. Safety assessment of inhaled xylitol in subjects with cystic fibrosis. J Cyst Fibros. 2007 Jan;6(1):31-4. doi: 10.1016/j.jcf.2006.05.002. Epub 2006 Jun 15.
PubMed 16781897Durairaj L, Neelakantan S, Launspach J, Watt JL, Allaman MM, Kearney WR, Veng-Pedersen P, Zabner J. Bronchoscopic assessment of airway retention time of aerosolized xylitol. Respir Res. 2006 Feb 16;7(1):27. doi: 10.1186/1465-9921-7-27.
PubMed 16483382Brown CL, Graham SM, Cable BB, Ozer EA, Taft PJ, Zabner J. Xylitol enhances bacterial killing in the rabbit maxillary sinus. Laryngoscope. 2004 Nov;114(11):2021-4. doi: 10.1097/01.mlg.0000147939.90249.47.
PubMed 15510034Durairaj L, Launspach J, Watt JL, Businga TR, Kline JN, Thorne PS, Zabner J. Safety assessment of inhaled xylitol in mice and healthy volunteers. Respir Res. 2004 Sep 16;5(1):13. doi: 10.1186/1465-9921-5-13.
PubMed 15377394Zabner J, Seiler MP, Launspach JL, Karp PH, Kearney WR, Look DC, Smith JJ, Welsh MJ. The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11614-9. doi: 10.1073/pnas.97.21.11614.
PubMed 11027360Holliday ZM, Launspach JL, Durairaj L, Singh PK, Zabner J, Stoltz DA. Effects of Tham Nasal Alkalinization on Airway Microbial Communities: A Pilot Study in Non-CF and CF Adults. Ann Otol Rhinol Laryngol. 2022 Sep;131(9):1013-1020. doi: 10.1177/00034894211051814. Epub 2021 Oct 21.
PubMed 34674574Hurley MN, Smith S, Forrester DL, Smyth AR. Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis. Cochrane Database Syst Rev. 2020 Jul 16;7(7):CD008037. doi: 10.1002/14651858.CD008037.pub4.
PubMed 32671834Singh S, Hornick D, Fedler J, Launspach JL, Teresi ME, Santacroce TR, Cavanaugh JE, Horan R, Nelson G, Starner TD, Zabner J, Durairaj L. Randomized controlled study of aerosolized hypertonic xylitol versus hypertonic saline in hospitalized patients with pulmonary exacerbation of cystic fibrosis. J Cyst Fibros. 2020 Jan;19(1):108-113. doi: 10.1016/j.jcf.2019.06.016. Epub 2019 Jul 18.
PubMed 31327670
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Study of Aerosolized Hypertonic Xylitol Versus Hypertonic Saline in Hospitalized Patients With Exacerbation of Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT00928135
- Acronym / sponsor ID
- 200901713
- Conditions
- Cystic Fibrosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Joseph ZabnerUniversity, hospital or other
- Study start
- 22 Jan 2013 (actual)
- Primary completion
- 9 Apr 2018 (actual)
- Study completion
- 9 Apr 2018 (actual)
- First posted
- 25 Jun 2009 (estimated)
- Results
- Posted 25 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 7% Hypertonic saline | Active comparator | Drug: Hypertonic saline5 ml of 7% saline twice daily |
| Hypertonic xylitol | Experimental | Drug: Xylitol5 ml of 15% xylitol twice daily |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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,
Key exclusion criteria (12 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Xylitol15% xylitol solution for aerosol; Dosage: 5 ml twice a day (BID) | Drug | Hypertonic xylitol |
| Hypertonic saline7% hypertonic saline solution for aerosol; Dosage: 5 ml twice a day (BID) | Drug | 7% Hypertonic saline |
Primary outcome
Change in FEV1 Percentage Predicted From Baseline
Time frame: 14 days
Change in lung function (forced expiratory volume in 1 second) between baseline and Day 14
2 secondary outcomes
Density of Colonization of Pseudomonas Aeruginosa Per Gram of Sputum
Time frame: 14 days
Exacerbations During 6 Months Follow-up
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16781897Durairaj L, Launspach J, Watt JL, Mohamad Z, Kline J, Zabner J. Safety assessment of inhaled xylitol in subjects with cystic fibrosis. J Cyst Fibros. 2007 Jan;6(1):31-4. doi: 10.1016/j.jcf.2006.05.002. Epub 2006 Jun 15.
- Background: PubMed 16483382Durairaj L, Neelakantan S, Launspach J, Watt JL, Allaman MM, Kearney WR, Veng-Pedersen P, Zabner J. Bronchoscopic assessment of airway retention time of aerosolized xylitol. Respir Res. 2006 Feb 16;7(1):27. doi: 10.1186/1465-9921-7-27.
- Background: PubMed 15510034Brown CL, Graham SM, Cable BB, Ozer EA, Taft PJ, Zabner J. Xylitol enhances bacterial killing in the rabbit maxillary sinus. Laryngoscope. 2004 Nov;114(11):2021-4. doi: 10.1097/01.mlg.0000147939.90249.47.
- Background: PubMed 15377394Durairaj L, Launspach J, Watt JL, Businga TR, Kline JN, Thorne PS, Zabner J. Safety assessment of inhaled xylitol in mice and healthy volunteers. Respir Res. 2004 Sep 16;5(1):13. doi: 10.1186/1465-9921-5-13.
- Background: PubMed 11027360Zabner J, Seiler MP, Launspach JL, Karp PH, Kearney WR, Look DC, Smith JJ, Welsh MJ. The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11614-9. doi: 10.1073/pnas.97.21.11614.
- Derived from this study: PubMed 34674574Holliday ZM, Launspach JL, Durairaj L, Singh PK, Zabner J, Stoltz DA. Effects of Tham Nasal Alkalinization on Airway Microbial Communities: A Pilot Study in Non-CF and CF Adults. Ann Otol Rhinol Laryngol. 2022 Sep;131(9):1013-1020. doi: 10.1177/00034894211051814. Epub 2021 Oct 21.
- Derived from this study: PubMed 32671834Hurley MN, Smith S, Forrester DL, Smyth AR. Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis. Cochrane Database Syst Rev. 2020 Jul 16;7(7):CD008037. doi: 10.1002/14651858.CD008037.pub4.
- Derived from this study: PubMed 31327670Singh S, Hornick D, Fedler J, Launspach JL, Teresi ME, Santacroce TR, Cavanaugh JE, Horan R, Nelson G, Starner TD, Zabner J, Durairaj L. Randomized controlled study of aerosolized hypertonic xylitol versus hypertonic saline in hospitalized patients with pulmonary exacerbation of cystic fibrosis. J Cyst Fibros. 2020 Jan;19(1):108-113. doi: 10.1016/j.jcf.2019.06.016. Epub 2019 Jul 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Zabner, M.D. principal investigator
PMID: 16781897
Lakshmi Durairaj, M.D. study director
PMID: 16781897
Jan L Launspach, R.N., CCRC study chair
PMID: 16781897
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Xylitol and Hypertonic saline in people with Cystic Fibrosis, run by Joseph Zabner at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in FEV1 Percentage Predicted From Baseline (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00928135, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2021.