Efficacy of Amiloride and Hypertonic Saline in Cystic Fibrosis

The purpose of this research study is to determine whether the combination of inhaled amiloride and a concentrated salt solution is better than the salt solution itself for cystic fibrosis (CF) patients. In CF, airway secretions are thick and dehydrated. Many patients use inhaled salt solutions to help draw water into their secretions so that they are easier to get rid of with chest physiotherapy ("chest PT") and cough. Unfortunately, these salt solutions are reabsorbed very quickly by the airways, so the beneficial effects may not last very long. In the hopes of prolonging their effects, the drug amiloride could be used in combination to slow salt and water reabsorption from airways. Amiloride is a medication that has been given by mouth for high blood pressure for many years. It is possible that the combination of salt solutions and inhaled amiloride may significantly improve the clearance of secretions in CF, which would be expected to improve lung function in CF.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: 7% NaCl; Drug: Amiloride HCl

• Study Type: Interventional
• Enrollment: 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Established diagnosis of CF
• 2 gene mutations identified, or
• Sweat chloride > 60 mmol/L, and
• 1 or more typical CF clinical features
• Age > 14 years
• Able to perform spirometry and have post-bronchodilator FEV1 > 50% of predicted at screening
• Oxyhemoglobin saturation (by pulse oximetry) > 92% on room air
• Able to provide informed consent

Exclusion Criteria:

• Unstable lung disease:
• FEV1 > 15% below best clinical measurement within 6 months
• Requirement for IV antibiotics within 4 weeks of screening
• Requirement for any change in pulmonary medication within 2 weeks of screening
• Evidence of reactive airways

• Clinical diagnosis of asthma

  -> 15% increase in FEV1 after bronchodilator at screening

• Hypertonic saline use within 2 weeks of screening
• Unwilling or unable to either continue or discontinue cyclical therapies (e.g. inhaled tobramycin) for the 2 weeks prior to screening and the entire study period
• Pregnancy, breast-feeding, or unwillingness to use barrier contraception during the entire study period
• History of allergy or intolerance to amiloride, hypertonic saline, quinine, albuterol, or related compounds
• Renal insufficiency (creatinine > 1.5 mg/dl)
• Hyperkalemia (K+ > 5.0 meq/L)
• Investigational drug use within 30 days of screening
• Radiation exposure within the past year that would exceed Federal Regulations by participating in the study

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
FEV1

Secondary Outcome Measures

Outcome Measure
Quality of Life
Mucociliary clearance rate
FVC
FEF25-75
Cough clearance rate

Collaborators and Investigators

• Sponsor: University of North Carolina
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Scott H. Donaldson, MD, University of North Carolina

Study record dates

Study Major Dates

• Study Start: July 1, 2001
• Primary Completion: December 7, 2022
• Study Completion: April 1, 2004

Study Registration Dates

• First Submitted: January 9, 2006
• First Submitted That Met QC Criteria: January 9, 2006
• First Posted (Estimate): January 10, 2006

Study Record Updates

• Last Update Posted (Estimate): January 10, 2006
• Last Update Submitted That Met QC Criteria: January 9, 2006
• Last Verified: December 1, 2005

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Channel Blockers; Diuretics, Potassium Sparing; Acid Sensing Ion Channel Blockers; Epithelial Sodium Channel Blockers; Amiloride
• Other Study ID Numbers: DONALDS00A0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No