Clinical trial NCT01002534: Does a Nasal Instillation of Vardenafil Normalize the Nasal Potential Difference in Cystic Fibrosis Patients?
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Vardenafil
Nasal instillation
Nasal Potential difference
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2009-10-27
Enrollment: 5
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cumulated changes in response to Chloride-free solution and isoproterenol (reflecting chloride transport)
timeFrame: Change from baseline (visit 1) and placebo to Vardenafil instillation
Secondary outcomes:
measure: Change in basal voltage value and in amiloride response (reflecting sodium transport)
timeFrame: Change from baseline (visit1) and placebo to Vardenafil instillation
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques universitaires St. Luc
Study officials:
affiliation: Cliniques universitaires St.Luc (Université catholique de Louvain)
name: Patrick LEBECQUE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cliniques universitaires St.Luc ( Université Catholique de Louvain)
name: Teresinha LEAL, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cliniques universitaires St.Luc (Université Catholique de Louvain)
name: Anissa LEONARD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dormer RL, Harris CM, Clark Z, Pereira MM, Doull IJ, Norez C, Becq F, McPherson MA. Sildenafil (Viagra) corrects DeltaF508-CFTR location in nasal epithelial cells from patients with cystic fibrosis. Thorax. 2005 Jan;60(1):55-9. doi: 10.1136/thx.2003.019778.
citation: Lubamba B, Lecourt H, Lebacq J, Lebecque P, De Jonge H, Wallemacq P, Leal T. Preclinical evidence that sildenafil and vardenafil activate chloride transport in cystic fibrosis. Am J Respir Crit Care Med. 2008 Mar 1;177(5):506-15. doi: 10.1164/rccm.200703-344OC. Epub 2007 Nov 15.