Aerosolized Hypertonic Xylitol Versus Hypertonic Saline in Cystic Fibrosis (CF) Subjects

NCT00928135 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 200901713
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Change in FEV1 Percentage Predicted From Baseline

  Change in lung function (forced expiratory volume in 1 second) between baseline and Day 14

  14 days

Secondary Outcomes (2)

• Density of Colonization of Pseudomonas Aeruginosa Per Gram of Sputum

  14 days

• Exacerbations During 6 Months Follow-up

  6 months

Study Arms (2)

7% Hypertonic saline

ACTIVE COMPARATOR

5 ml of 7% saline twice daily

Drug: Hypertonic saline

Hypertonic xylitol

EXPERIMENTAL

5 ml of 15% xylitol twice daily

Drug: Xylitol

Interventions

Xylitol DRUG

15% xylitol solution for aerosol; Dosage: 5 ml twice a day (BID)

Hypertonic xylitol

Hypertonic saline DRUG

7% hypertonic saline solution for aerosol; Dosage: 5 ml twice a day (BID)

7% Hypertonic saline

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Joseph Zabner: lead

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (8)

• 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.

  PMID: 16781897 BACKGROUND

• Durairaj 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.

  PMID: 16483382 BACKGROUND

• Brown 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.

  PMID: 15510034 BACKGROUND

• Durairaj 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.

  PMID: 15377394 BACKGROUND

• Zabner 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.

  PMID: 11027360 BACKGROUND

• Holliday 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.

  PMID: 34674574 DERIVED

• Hurley 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.

  PMID: 32671834 DERIVED

• Singh 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.

  PMID: 31327670 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Xylitol; Saline Solution, Hypertonic

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Hypertonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Lakshmi Durairaj
• Organization: University of Iowa

lakshmi-durairaj@uiowa.edu

3193537968

Study Officials

• Joseph Zabner, M.D.

  PMID: 16781897

  PRINCIPAL INVESTIGATOR

• Lakshmi Durairaj, M.D.

  PMID: 16781897

  STUDY DIRECTOR

• Jan L Launspach, R.N., CCRC

  PMID: 16781897

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 18, 2009
• First Posted: June 25, 2009
• Study Start: January 22, 2013
• Primary Completion: April 9, 2018
• Study Completion: April 9, 2018
• Last Updated: June 25, 2021
• Results First Posted: June 25, 2021

Record last verified: 2020-10

Locations

US (1)