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

Cystic Fibrosis Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01002534
• Other study ID #: VARD-99
• Status: Terminated
• Phase: Phase 2
• Start date: October 2011
• Est. completion date: March 2018

Study information

• Verified date: February 2019
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: March 2018
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Vardenafil
Nasal instillation of Vardenafil
• Placebo
Nasal instillation of placebo matching in appearance with the Vardenafil instillation

Locations

Country	Name	City	State
Belgium	Cliniques universitaires St. Luc	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

References & Publications (2)

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. — View 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. Epub 2007 Nov 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulated changes in response to Chloride-free solution and isoproterenol (reflecting chloride transport)		Change from baseline (visit 1) and placebo to Vardenafil instillation
Secondary	Change in basal voltage value and in amiloride response (reflecting sodium transport)		Change from baseline (visit1) and placebo to Vardenafil instillation