Effect of Hypertonic Saline on Mucus Clearance in Children Ages 5-12 With Cystic Fibrosis

NCT01031706 | Completed Results DMC

• 2 other identifiers: 09-12581P50HL084934
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Previous work demonstrated that inhaled hypertonic saline (HS) reduces exacerbation frequency and improves lung function in adults with cystic fibrosis (CF). It is unclear, however, whether HS will benefit young patients suffering from CF. The investigators propose to further support the concept that HS can benefit children with mild CF lung disease by performing a relatively short, placebo controlled study of HS in 5-12 year olds, using lung function and mucociliary clearance as key outcome measures.

Conditions

Cystic Fibrosis

Keywords

Hypertonic Saline; Pediatrics; Cystic Fibrosis; Mucociliary Clearance; Lung Clearance Index

Outcome Measures

Primary Outcomes (1)

• Change in Mucociliary Clearance Rate

  Average radio tracer clearance through 90 minutes (MCC90) is primary index of mucociliary clearance at each study. Primary study outcome: is absolute change in MCC90 between baseline and at end of treatment (where MCC measured 8-12 hours after final dose of study drug) - reflects sustained impact on MCC

  Baseline versus after completion of 4 week treatment period

Secondary Outcomes (1)

• FEV1 (Spirometry) Change

  Baseline and after 4 weeks of treatment

Study Arms (2)

Hypertonic saline

EXPERIMENTAL

6% NaCl, 4 ml TID via eFlow

Drug: Hypertonic Saline

Placebo

PLACEBO COMPARATOR

0.12% x 4ml via eFlow nebulizer

Drug: Placebo

Interventions

Hypertonic Saline DRUG

inhaled HS (6% NaCl, 4mL) three times a day for 28 days

Also known as: HS

Hypertonic saline

Placebo DRUG

4 ml 0.12% NaCl inhaled three times a day x 28 days

Also known as: .12% NaCl

Placebo

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gender: Females or Males. If the subject is female and of childbearing potential (first menses has occurred), she must have a documented negative pregnancy test at screening and prior to each mucociliary clearance study. Those of childbearing potential must be abstinent or using an acceptable method of birth control (i.e. an Intrauterine Contraceptive Device with a failure rate of \<1%, hormonal contraceptives or a barrier method).
• Age: 5-12 years, inclusive
• Diagnosis: Cystic fibrosis documented by a compatible clinical presentation and sweat chloride \> 60 mEq/l or 2 disease causing CFTR mutations.
• Severity of the Disease: Suitable patients will have mild lung disease, as defined by:
• Pulmonary Function: Each patient must have an FEV1 of greater than or equal to 60% of predicted at the screening visit.
• Hemoglobin saturation: Patients must have an oxygen saturation of \>92% on room air as determined by pulse oximetry at the screening visit.
• Informed consent - The patient and a parent or legally authorized guardian must agree to the subject's participation in the study by signing and dating the informed consent/assent forms after the nature of the study has been fully explained and all questions have been satisfactorily answered.

You may not qualify if:

• Unstable or asthmatic 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. Patients with a history of co-existent asthma, as manifested by wheezing and significant bronchoreactivity (\>15% increase in FEV1 with bronchodilator), will also be excluded.
• Other medication usage: Patients unable or unwilling to be withdrawn from hypertonic saline therapy for two weeks prior to Visit 1 (baseline MCC visit). Patients using Pulmozyme will be permitted to participate in this trial. Patients on chronic, cycling antibiotics will be required to have completed at least 2 full cycles of the prescribed antibiotic prior to enrollment and should not cycle on or off this therapy during the treatment period of the study.
• Spirometry Performance: Those subjects who are unable to perform acceptable, reproducible spirometry will be excluded from this study.
• Drug allergy: A history of allergy or intolerance to any of the study medications, including albuterol or hypertonic saline.
• Have received an investigational drug or therapy during the preceding 30 days.
• 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
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (8)

• 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

• 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

• 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

• Matsui H, Grubb BR, Tarran R, Randell SH, Gatzy JT, Davis CW, Boucher RC. Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell. 1998 Dec 23;95(7):1005-15. doi: 10.1016/s0092-8674(00)81724-9.

  PMID: 9875854 BACKGROUND

• Tarran R. Regulation of airway surface liquid volume and mucus transport by active ion transport. Proc Am Thorac Soc. 2004;1(1):42-6. doi: 10.1513/pats.2306014.

  PMID: 16113411 BACKGROUND

• Elkins MR, Bye PT. Inhaled hypertonic saline as a therapy for cystic fibrosis. Curr Opin Pulm Med. 2006 Nov;12(6):445-52. doi: 10.1097/01.mcp.0000245714.89632.b2.

  PMID: 17053496 BACKGROUND

• Modi AC, Quittner AL. Validation of a disease-specific measure of health-related quality of life for children with cystic fibrosis. J Pediatr Psychol. 2003 Dec;28(8):535-45. doi: 10.1093/jpepsy/jsg044.

  PMID: 14602844 BACKGROUND

• Donaldson SH, Danielle Samulski T, LaFave C, Zeman K, Wu J, Trimble A, Ceppe A, Bennett WD, Davis SD. A four week trial of hypertonic saline in children with mild cystic fibrosis lung disease: Effect on mucociliary clearance and clinical outcomes. J Cyst Fibros. 2020 Nov;19(6):942-948. doi: 10.1016/j.jcf.2020.07.009. Epub 2020 Jul 12.

  PMID: 32669217 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

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)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Scott H. Donaldson
• Organization: University of North Carolina at Chapel Hill

scott_donaldson@med.unc.edu

919-966-9198

Study Officials

• Scott H Donaldson, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 11, 2009
• First Posted: December 15, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: March 3, 2017
• Results First Posted: June 30, 2014

Record last verified: 2014-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)