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

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Status and phase: Terminated; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: Placebo; Drug: Vardenafil

Study type: Interventional

Funder types: Other

Identifiers

NCT01002534

VARD-99

Details and patient eligibility

About

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

Full 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.

Enrollment: 5 patients

Sex: All

Ages: 14+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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5 participants in 3 patient groups, including a placebo group

baseline

No Intervention group

Description:

visit 1

Vardenafil

Active Comparator group

Description:

nasal instillation of Vardenafil ( visit 2 or 3)

Treatment:

Drug: Vardenafil

Placebo

Placebo Comparator group

Description:

Nasal instillation of placebo (visit 3 or 2)

Treatment:

Drug: Placebo