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

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.

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01002534

Enrollment

Registered

2009-10-27

Start date

2011-10-31

Completion date

2018-03-31

Last updated

2019-02-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis, Vardenafil, Nasal instillation, Nasal Potential difference

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.

Interventions

DRUGVardenafil

Nasal instillation of Vardenafil

DRUGPlacebo

Nasal instillation of placebo matching in appearance with the Vardenafil instillation

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

14 Years to No maximum

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

Design outcomes

Primary

Measure	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

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

Countries

Belgium

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026