Durability of Hypertonic Saline for Enhancing Mucociliary Clearance in Cystic Fibrosis

NCT01094704 | Completed Phase 1 Results

• 1 other identifier: 09-0670
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

Direct measurement of mucociliary and cough clearance (MCC/CC) has been used as a biomarker in cystic fibrosis (CF). Additional knowledge of the performance of this biomarker is needed to inform exploratory clinical trial design in support of programs to develop new inhaled therapies for CF. We hypothesize that MCC/CC measurements can be used to determine the durability of action of agents like hypertonic saline (HS) which increase epithelial lining fluid height.

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; mucociliary clearance; hypertonic saline

Outcome Measures

Primary Outcomes (1)

• Change in Average Mucociliary Clearance (0-90 Minutes) at 1 and 4 Hrs Post Dose (MCC4hr - MCCbaseline; MCC1hr - MCCbaseline)

  Duration of action of hypertonic saline as determined by measurements of mucociliary clearance/cough clearance 4 hours post dose.

  1-4 hours post-dose

Study Arms (2)

Hypertonic Saline - 1 hour

EXPERIMENTAL

sodium chloride (7%); mucociliary clearance measured 1 hour post dose

Drug: sodium chloride (7%)

Hypertonic Saline - 4 hours

EXPERIMENTAL

sodium chloride (7%); mucociliary clearance measured four hours post-dose.

Drug: sodium chloride (7%)

Interventions

sodium chloride (7%) DRUG

4mL nebulized 7% sodium chloride

Also known as: Hyper-Sal, Hypertonic saline (7%)

Hypertonic Saline - 1 hour; Hypertonic Saline - 4 hours

Eligibility Criteria

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

You may qualify if:

• Gender: Male or female (non-pregnant, non-lactating)
• Cystic fibrosis documented by a compatible clinical and radiographic presentation, and sweat chloride \> 60 mEq/l or 2 disease causing CFTR mutations.
• Severity of Disease:
• Must have FEV1 of greater than or equal to 50% of predicted at the screening visit.
• Must have an oxygen saturation of \>92% on room air as determined by pulse oximetry at the screening visit.
• Patient or legally authorized representative agrees to the patient/individual's participation in the study by signing and dating the informed consent form after the nature of the study has been fully explained and all questions have been satisfactorily answered.

You may not qualify if:

• Unstable lung disease: As defined by a change in medical regimen during the preceding 2 weeks; an FEV1 \>15% below recent (within 6 months) clinical measurements; or a significant new finding on chest radiograph (pneumothorax, lobar/segmental collapse) not considered a part of the usual, chronic progression of CF lung disease.
• Patients unable or unwilling to be withdrawn from hypertonic saline therapy, dornase alfa, or N-acetylcysteine 3 days prior to and for the duration of each Baseline and Treatment Period will be excluded.
• Patients unable to withhold use of long-acting bronchodilators (i.e., Salmeterol, Advair, Formoterol), anti-cholinergics, and vest therapy 12 hours prior to and for the duration of each treatment period.
• Patients unable to withhold short-acting bronchodilator 6 hours prior to and for the duration of each treatment period except as prescribed by the study protocol.
• Patients that have received an investigational drug or therapy during the preceding 30 days.
• Patients that have had radiation exposure within the past year that would cause them to exceed Federal Regulations by participating in this study.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Johns Hopkins University: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (2)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27516, United States

Location

Related Publications (7)

• Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med. 2006 Jan 19;354(3):241-50. doi: 10.1056/NEJMoa043891.

  PMID: 16421365 BACKGROUND

• Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900.

  PMID: 16421364 BACKGROUND

• Bennett WD, Olivier KN, Zeman KL, Hohneker KW, Boucher RC, Knowles MR. Effect of uridine 5'-triphosphate plus amiloride on mucociliary clearance in adult cystic fibrosis. Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1796-801. doi: 10.1164/ajrccm.153.6.8665037.

  PMID: 8665037 BACKGROUND

• Donaldson SH, Boucher RC. Sodium channels and cystic fibrosis. Chest. 2007 Nov;132(5):1631-6. doi: 10.1378/chest.07-0288.

  PMID: 17998363 BACKGROUND

• Pons G, Marchand MC, d'Athis P, Sauvage E, Foucard C, Chaumet-Riffaud P, Sautegeau A, Navarro J, Lenoir G. French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group. Pediatr Pulmonol. 2000 Jul;30(1):25-31. doi: 10.1002/1099-0496(200007)30:13.0.co;2-c.

  PMID: 10862159 BACKGROUND

• Sood N, Bennett WD, Zeman K, Brown J, Foy C, Boucher RC, Knowles MR. Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects. Am J Respir Crit Care Med. 2003 Jan 15;167(2):158-63. doi: 10.1164/rccm.200204-293OC. Epub 2002 Oct 31.

  PMID: 12411282 BACKGROUND

• Wark P, McDonald VM, Smith S. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD001506. doi: 10.1002/14651858.CD001506.pub5.

  PMID: 37319354 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Sodium Chloride; 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)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Hypertonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Scott Donaldson
• Organization: UNC-Chapel Hill

scott_donaldson@med.unc.edu

919-966-9198

Study Officials

• William Bennett, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 19, 2010
• First Posted: March 29, 2010
• Study Start: November 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: August 21, 2012
• Results First Posted: August 21, 2012

Record last verified: 2012-08

Locations

US (2)