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

This study has been completed.
Sponsor:
Information provided by:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier:
NCT00945347
First received: July 23, 2009
Last updated: August 9, 2011
Last verified: August 2011
  Purpose

The purpose of this study is to investigate within a short delay the effect of nasal instillation of Miglustat on nasal potential difference in cystic fibrosis patients homozygous for the F508del mutation.


Condition Intervention Phase
Cystic Fibrosis
Drug: Miglustat
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 Miglustat 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:
  • change in response to Chloride-free solution and isoproterenol ( reflecting chloride transport) [ Time Frame: change from baseline ( visit 1) and placebo to miglustat 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 miglustat instillation ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: July 2009
Study Completion Date: June 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Baseline
Visit 1
Active Comparator: Miglustat
Nasal instillation of Miglustat (visit 2 or 3)
Drug: Miglustat
Nasal instillation of miglustat
Placebo Comparator: Placebo
Nasal instillation of placebo (visit 3 or 2)
Drug: Placebo
Nasal instillation of placebo matching in appearance with the Miglustat instillation

Detailed Description:

Miglustat is an inhibitor of α-glucosidases and other enzymes. Oral miglustat is currently marketed in Europa and US for the treatment of Gaucher type 1 patients for whom enzyme replacement treatment is not an option.

Gastro-intestinal side effects are common with this formulation. This medication has been shown to have a beneficial effect both on Cl- an Na+ transports in cystic fibrosis epithelial cells. In addition, a single airway delivery of low-dose Miglustat normalizes nasal potential difference (NPD) in F508del cystic fibrosis mice. NPD abnormalities specific of CF patients are considered to reflect the primary defect of CFTR protein so that any curative treatment is expected to correct them at least partially.

In the field of respiratory pharmacology, it is a general rule that the inhaled route is to be favoured whenever possible : it is usually more effective despite much lower doses and systemic absorption (which also implies lower costs and improved tolerance).

The aim of this study is to investigate the effect of a single local administration of Miglustat 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 genetic test
  • Aged 14 years and older
  • Male or female (non-pregnant women who are to remain non-pregnant for 3 months after the end of the study)
  • 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 such as respiratory tract infection
  • Active or passive smoking
  • Allergic chronic rhinitis
  • History of significant lactose intolerance
  • History of neuropathy
  • History of cataracts or known increased risk of cataract formation
  • Hypersensitivity to miglustat or any excipients
  • 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: NCT00945347

Locations
Belgium
Cliniques Universitaires St Luc (Université Catholique de Louvain) 10 avenue Hippocrate
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)
  More Information

Publications:
Responsible Party: Patrick Lebecque, MD, PhD, Cliniques universitaires Saint Luc (Université Catholique de Louvain)
ClinicalTrials.gov Identifier: NCT00945347     History of Changes
Other Study ID Numbers: MIG-99
Study First Received: July 23, 2009
Last Updated: August 9, 2011
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
Cystic fibrosis
miglustat
nasal instillation
nasal potential difference

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Miglustat
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014