Durability of Hypertonic Saline for Enhancing Mucociliary Clearance in Cystic Fibrosis

2014-08-27 03:14:57 | BioPortfolio


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.


A reduction in epithelial lining fluid height in cystic fibrosis (CF) as a consequence of decreased function of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride channel and related increased activity of the Epithelial sodium (Na) Channel (ENaC) results in impaired mucociliary clearance (MCC), mucus stasis, inflammation, infection, and ultimately progressive bronchiectasis. Inhalation of hypertonic saline (HS), through a direct osmotic effect on the airways, results in an increase in epithelial lining fluid height in vitro and an increase in MCC in vivo as measured following inhalation of a radiotracer with gamma scintigraphy (Sood, et al 2003). MCC as a biomarker is being validated in the clinic, as administration of inhaled hypertonic saline (HS) to cystic fibrosis patients results in short- and medium-term improvements in MCC (Donaldson, et al 2006), while long-term administration of HS is associated with improvements in the registration endpoints of lung function and pulmonary exacerbations (Elkins, et al 2006). Based in large part on these studies, HS has gained acceptance in the CF community, with estimates of up to 50% of patients being treated with this therapy. MCC/CC is thus an excellent choice as a Proof of Concept endpoint for exploratory clinical studies of ENaC modulators. Prior clinical experience with the ENaC blocker amiloride, which improves MCC acutely in healthy volunteers (Sood, et al 2003) but failed to improve lung function in long-term studies in CF (Pons, et al 2000), suggests that durable ENaC modulation will be required for clinical success. It is believed that modulation of ENaC for a period of at least 4 hours will be required to achieve the necessary durability. This durability should also enable twice daily dosing. For comparison we need to know the effectiveness of HS over this same period. Thus, this study is intended to assess 1) the duration of action out to 4 hours for inhaled hypertonic saline (7%) in adult CF patients and 2) the variability of MCC/CC measurements with and without HS treatment. These assessments at UNC will be compared to similar measures at Johns Hopkins University (JHU) for Novartis to determine the feasibility for future multicenter studies using MCC/CC as a primary endpoint.

Study Design

Allocation: Randomized, Control: Uncontrolled, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment


Cystic Fibrosis


sodium chloride (7%)


Johns Hopkins University
United States




University of North Carolina, Chapel Hill

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:14:57-0400

Clinical Trials [1922 Associated Clinical Trials listed on BioPortfolio]

Effects of Inhaled Bicarbonate on Airway pH in Cystic Fibrosis

This study will compare the use of inhaled concentrated sodium chloride solution to an inhaled solution of sodium bicarbonate in an attempt to decrease the thickness and stickiness of the ...

Inhaled Sodium Pyruvate for the Treatment of Cystic Fibrosis.

It is hypothesized that the inhalation of sodium pyruvate will reduce lung damage in patients with Cystic Fibrosis (CF) by its ability to reduce levels of toxic reactive oxygen and nitroge...

Examination of the Lipid Metabolism of the Liver After Choline Substitution in Cystic Fibrosis

Pilot study to investigate the effect of choline chloride in cystic fibrosis patients with liver steatosis by comparing their status before and after the intervention

Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium

The purpose of the trial is to investigate if the use of inhaled colistimethate sodium administered twice daily for 12 months delays the time to the first pulmonary exacerbation compared t...

A Phase I Study of Inhaled Sodium Pyruvate for the Treatment of Cystic Fibrosis.

The primary objective of this study is to assess the safety of inhaled sodium pyruvate in people with Cystic Fibrosis (CF). Further, to determine whether inhaled sodium pyruvate will impro...

PubMed Articles [4104 Associated PubMed Articles listed on BioPortfolio]

Chloride and sodium ion concentrations in saliva and sweat as a method to diagnose cystic fibrosis.

Cystic fibrosis diagnosis is dependent on the chloride ion concentration in the sweat test (≥60mEq/mL - recognized as the gold standard indicator for cystic fibrosis diagnosis). Moreover, the saliva...

SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum.

In healthy lungs, epithelial sodium channel (ENaC) is regulated by short, palate, lung, and nasal clone 1 (SPLUNC1). In cystic fibrosis (CF), ENaC is hyperactivated in part due to a loss of SPLUNC1 fu...

miRNA as a bullet against cystic fibrosis.

Cystic fibrosis is the most common lethal genetic disease in the Caucasian population, characterized by CFTR gene mutations, which is a chloride channel. Whereas this gene has been known since 1989, t...

Interventions for the eradication of meticillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis.

Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function de...

No easy road to better cystic fibrosis care in Eastern Europe?

Medical and Biotech [MESH] Definitions

A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)

An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.

A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.

A subclass of symporters that specifically transport SODIUM CHLORIDE and POTASSIUM CHLORIDE across cellular membranes in a tightly coupled process.

Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.

More From BioPortfolio on "Durability of Hypertonic Saline for Enhancing Mucociliary Clearance in Cystic Fibrosis"

Quick Search


Relevant Topics

Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

Searches Linking to this Trial