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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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 or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Miglustat; Drug: Placebo	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	10 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Triple (Participant, Care Provider, 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.
Study Start Date :	July 2009
Actual Primary Completion Date :	May 2011
Actual Study Completion Date :	June 2011

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. 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 Outcome Measures :

1. change in basal voltage value and in amiloride response ( reflecting sodium transport) [ Time Frame: change from baseline (visit1) and placebo to miglustat instillation ]

Eligibility Criteria

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Ages Eligible for Study:	14 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Lubamba B, Lebacq J, Lebecque P, Vanbever R, Leonard A, Wallemacq P, Leal T. Airway delivery of low-dose miglustat normalizes nasal potential difference in F508del cystic fibrosis mice. Am J Respir Crit Care Med. 2009 Jun 1;179(11):1022-8. doi: 10.1164/rccm.200901-0049OC. Epub 2009 Mar 19.

Norez C, Noel S, Wilke M, Bijvelds M, Jorna H, Melin P, DeJonge H, Becq F. Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the alpha-glucosidase inhibitor miglustat. FEBS Lett. 2006 Apr 3;580(8):2081-6. Epub 2006 Mar 10.

Noël S, Wilke M, Bot AG, De Jonge HR, Becq F. Parallel improvement of sodium and chloride transport defects by miglustat (n-butyldeoxynojyrimicin) in cystic fibrosis epithelial cells. J Pharmacol Exp Ther. 2008 Jun;325(3):1016-23. doi: 10.1124/jpet.107.135582. Epub 2008 Feb 28.

Norez C, Antigny F, Noel S, Vandebrouck C, Becq F. A cystic fibrosis respiratory epithelial cell chronically treated by miglustat acquires a non-cystic fibrosis-like phenotype. Am J Respir Cell Mol Biol. 2009 Aug;41(2):217-25. doi: 10.1165/rcmb.2008-0285OC. Epub 2009 Jan 8.

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
First Posted:	July 24, 2009
Last Update Posted:	August 10, 2011
Last Verified:	August 2011

Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:

Cystic fibrosis; miglustat; 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; Miglustat	1-Deoxynojirimycin; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Physiological Effects of Drugs