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

Cliniques universitaires Saint-Luc- Université Catholique de Louvain10 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Cystic Fibrosis

Interventions

MiglustatDRUG

Nasal instillation of miglustat

PlaceboDRUG

Nasal instillation of placebo matching in appearance with the Miglustat instillation

Eligibility

Sex: ALLMin age: 14 Years

Medical Language ↔ Plain English

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

Locations (1)

Cliniques Universitaires St Luc (Université Catholique de Louvain) 10 avenue Hippocrate

Brussels, Belgium

Outcomes

Primary Outcomes

change in response to Chloride-free solution and isoproterenol ( reflecting chloride transport)

Time frame: change from baseline ( visit 1) and placebo to miglustat instillation

Secondary Outcomes

change in basal voltage value and in amiloride response ( reflecting sodium transport)

Time frame: change from baseline (visit1) and placebo to miglustat instillation

Data from ClinicalTrials.gov

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