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

This study has suspended participant recruitment.
(not yet started)
Sponsor:
Information provided by (Responsible Party):
Anissa Léonard, Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier:
NCT01002534
First received: October 26, 2009
Last updated: June 6, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Cystic Fibrosis
Drug: Vardenafil
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:

Primary Outcome Measures:
  • Cumulated changes in response to Chloride-free solution and isoproterenol (reflecting chloride transport) [ Time Frame: Change from baseline (visit 1) and placebo to Vardenafil instillation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in basal voltage value and in amiloride response (reflecting sodium transport) [ Time Frame: Change from baseline (visit1) and placebo to Vardenafil instillation ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: October 2011
Estimated Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01002534

Locations
Belgium
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)
  More Information

Publications:
Responsible Party: Anissa Léonard, Dr, Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT01002534     History of Changes
Other Study ID Numbers: VARD-99
Study First Received: October 26, 2009
Last Updated: June 6, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
Cystic Fibrosis
Vardenafil
Nasal instillation
Nasal Potential difference

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Vardenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on October 01, 2014