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

Phase 2

Terminated

• Conditions: Cystic Fibrosis
• Interventions: Drug: Placebo; Drug: Vardenafil

• Registration Number: NCT01002534
• Lead Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2009-10-26
• Study First Submitted QC: 2009-10-26
• Study First Posted: 2009-10-27
• Study Start: 2011-10
• Primary Completion: 2012-06
• Study Completion: 2018-03
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-21
• Last Update Posted: 2019-02-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Nasal instillation of placebo (visit 3 or 2)
Vardenafil	Vardenafil	nasal instillation of Vardenafil ( visit 2 or 3)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Change in basal voltage value and in amiloride response (reflecting sodium transport)	Change from baseline (visit1) and placebo to Vardenafil instillation

Trial Locations

Locations (1)

Cliniques universitaires St. Luc; 🇧🇪 Brussels, Belgium