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

Sponsor

Cliniques universitaires Saint-Luc- Université Catholique de Louvain (Other)

Overall Status

Terminated

CT.gov ID

NCT01002534

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Vardenafil Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 2011

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: baseline visit 1
Active Comparator: Vardenafil nasal instillation of Vardenafil ( visit 2 or 3)	Drug: Vardenafil Nasal instillation of Vardenafil
Placebo Comparator: Placebo Nasal instillation of placebo (visit 3 or 2)	Drug: Placebo Nasal instillation of placebo matching in appearance with the Vardenafil instillation

Arm

Intervention/Treatment

No Intervention: baseline

visit 1

Active Comparator: Vardenafil

nasal instillation of Vardenafil ( visit 2 or 3)

Drug: Vardenafil

Nasal instillation of Vardenafil

Placebo Comparator: Placebo

Nasal instillation of placebo (visit 3 or 2)

Drug: Placebo

Nasal instillation of placebo matching in appearance with the Vardenafil instillation

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cliniques universitaires St. Luc	Brussels		Belgium	1200

Sponsors and Collaborators

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Investigators

Principal Investigator: Patrick LEBECQUE, MD, PhD, Cliniques universitaires St.Luc (Université catholique de Louvain)
Principal Investigator: Teresinha LEAL, MD, PhD, Cliniques universitaires St.Luc ( Université Catholique de Louvain)
Principal Investigator: Anissa LEONARD, MD, Cliniques universitaires St.Luc (Université Catholique de Louvain)