Inhaled Xylitol Versus Saline in Stable Subjects With Cystic Fibrosis

NCT01355796 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 201209728
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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 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

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Change in FEV1 % Predicted From Baseline

  Change from baseline in FEV1(maximal amount of air you can forcefully exhale in one second) % predicted

  Baseline and 14 days

Secondary Outcomes (1)

• Sputum Density

  baseline and 14 days

Study Arms (2)

Aerosolized Hypertonic xyltiol

EXPERIMENTAL

Aerosolized xylitol (5 ml) twice daily for 14 days

Drug: Xylitol; Drug: Hypertonic saline

Hypertonic saline

ACTIVE COMPARATOR

Aerosolized 7% hypertonic saline (4 ml) twice daily for 14 days

Drug: Xylitol; Drug: Hypertonic saline

Interventions

Xylitol DRUG

Aerosolized 15% xylitol, 5 ml twice a day for 2 weeks

Also known as: Xylo-pentane-1, 2, 3, 4, 5-pentol

Aerosolized Hypertonic xyltiol; Hypertonic saline

Hypertonic saline DRUG

4 ml of 7 % saline aerosolized twice a day for 2 weeks

Also known as: 7% NaCl

Aerosolized Hypertonic xyltiol; Hypertonic saline

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Joseph Zabner: lead
• Ann & Robert H Lurie Children's Hospital of Chicago: collaborator
• Northwestern University: collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60614, United States

Location

Related Publications (15)

• Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005 May 12;352(19):1992-2001. doi: 10.1056/NEJMra043184. No abstract available.

  PMID: 15888700 BACKGROUND

• Zabner J, Smith JJ, Karp PH, Widdicombe JH, Welsh MJ. Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway epithelia in vitro. Mol Cell. 1998 Sep;2(3):397-403. doi: 10.1016/s1097-2765(00)80284-1.

  PMID: 9774978 BACKGROUND

• Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell. 1997 Feb 21;88(4):553-60. doi: 10.1016/s0092-8674(00)81895-4.

  PMID: 9038346 BACKGROUND

• Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, Wilson JM. Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest. 1998 Sep 1;102(5):874-80. doi: 10.1172/JCI2410.

  PMID: 9727055 BACKGROUND

• Travis SM, Conway BA, Zabner J, Smith JJ, Anderson NN, Singh PK, Greenberg EP, Welsh MJ. Activity of abundant antimicrobials of the human airway. Am J Respir Cell Mol Biol. 1999 May;20(5):872-9. doi: 10.1165/ajrcmb.20.5.3572.

  PMID: 10226057 BACKGROUND

• Makinen KK, Bennett CA, Hujoel PP, Isokangas PJ, Isotupa KP, Pape HR Jr, Makinen PL. Xylitol chewing gums and caries rates: a 40-month cohort study. J Dent Res. 1995 Dec;74(12):1904-13. doi: 10.1177/00220345950740121501.

  PMID: 8600188 BACKGROUND

• Soderling E, Makinen KK, Chen CY, Pape HR Jr, Loesche W, Makinen PL. Effect of sorbitol, xylitol, and xylitol/sorbitol chewing gums on dental plaque. Caries Res. 1989;23(5):378-84. doi: 10.1159/000261212.

  PMID: 2766327 BACKGROUND

• Makinen KK. Long-term tolerance of healthy human subjects to high amounts of xylitol and fructose: general and biochemical findings. Int Z Vitam Ernahrungsforsch Beih. 1976;15:92-104.

  PMID: 783060 BACKGROUND

• Uhari M, Kontiokari T, Koskela M, Niemela M. Xylitol chewing gum in prevention of acute otitis media: double blind randomised trial. BMJ. 1996 Nov 9;313(7066):1180-4. doi: 10.1136/bmj.313.7066.1180.

  PMID: 8916749 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

• Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BA, Greenberg EP, Valore EV, Welsh MJ, Ganz T, Tack BF, McCray PB Jr. Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14961-6. doi: 10.1073/pnas.95.25.14961.

  PMID: 9843998 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

• 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

• Marks JH, Hare KL, Saunders RA, Homnick DN. Pulmonary function and sputum production in patients with cystic fibrosis: a pilot study comparing the PercussiveTech HF device and standard chest physiotherapy. Chest. 2004 Apr;125(4):1507-11. doi: 10.1378/chest.125.4.1507.

  PMID: 15078765 BACKGROUND

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: Janice Launspach
• Organization: University of Iowa

janice-launspach@uiowa.edu

319-356-2047

Study Officials

• Joseph Zabner, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

• Lakshmi Durairaj, MD

  University of Iowa

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 16, 2011
• First Posted: May 18, 2011
• Study Start: May 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: October 24, 2018
• Results First Posted: September 4, 2018

Record last verified: 2018-09

Locations

US (2)