Does a Nasal Instillation of Vardenafil Normalize the Nasal Potential Difference in Cystic Fibrosis Patients?

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of a nasal instillation of Vardenafil on nasal potential difference in cystic fibrosis patients homozygous for the F508del mutation

Detailed Description
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CFTR protein has been shown to be an ohmic, small conductance channel regulated by cAMP intracellular levels that are balanced by degradation through cyclic nucleotide phosphodiesterases (PDE). Several families of PDEs with varying selectivities for cAMP and/or cGMP have been identified.PDE5 is highly specific for cGMP and is involved in the regulation of the intracellular concentration of cGMP in various tissues. Recently, it has been shown, in a preclinical model of transgenic mice, that pharmacological doses of sildenafil and vardenafil, two clinically approved PDE5 inhibitors, stimulate chloride transport activity of the mutant F508del-protein (Lubamba et al, 2008); this parameter has been assessed by means of the nasal potential difference (NPD). An increasing effect of sildenafil on the expression of F508del-CFTR protein (Dormer et al,2005) was originally reported in nasal epithelial cells harvested from patients with cystic fibrosis and cultured on impermeable supports, a configuration that allows interaction of drugs with the apical side of epithelia. This study aims at investigating the effect of a single local administration of vardenafil on NPD measurements in CF patients homozygous for the F508del mutation.

Official Title
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Does a Nasal Instillation of Vardenafil Normalize the Nasal Potential Difference in Cystic Fibrosis Patients Homozygous for the F508del Mutation? A Randomized, Double Blind, Placebo-controlled Study.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Vardenafil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cystic fibrosis patients homozygous for the F508del mutation as confirmed by a genetic test Aged 14 years and older Male and female FEV1 >50% of predicted normal Exclusion Criteria: Acute respiratory tract infection or pulmonary exacerbation requiring antibiotic intervention within 2 weeks of visit 1 Any condition prohibiting the correct measurement of the NPD Active or passive smoking Planned treatment or treatment with another investigational drug or therapy within 1 month prior to randomisation

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: baseline<br>visit 1 | |
| Active Comparator: Vardenafil<br>nasal instillation of Vardenafil ( visit 2 or 3) | Drug: Vardenafil<br>* Nasal instillation of Vardenafil<br>|
| Placebo Comparator: Placebo<br>Nasal instillation of placebo (visit 3 or 2) | Drug: Placebo<br>* Nasal instillation of placebo matching in appearance with the Vardenafil instillation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulated changes in response to Chloride-free solution and isoproterenol (reflecting chloride transport) |  | Change from baseline (visit 1) and placebo to Vardenafil instillation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in basal voltage value and in amiloride response (reflecting sodium transport) |  | Change from baseline (visit1) and placebo to Vardenafil instillation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, Vardenafil, Nasal instillation, Nasal Potential difference