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

Cystic Fibrosis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00945347
• Other study ID #: MIG-99
• Status: Completed
• Phase: Phase 2
• First received: July 23, 2009
• Last updated: August 9, 2011
• Start date: July 2009
• Est. completion date: June 2011

Study information

• Verified date: August 2011
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Miglustat
Nasal instillation of miglustat
• Placebo
Nasal instillation of placebo matching in appearance with the Miglustat instillation

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St Luc (Université Catholique de Louvain) 10 avenue Hippocrate	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in response to Chloride-free solution and isoproterenol ( reflecting chloride transport)		change from baseline ( visit 1) and placebo to miglustat instillation	No
Secondary	change in basal voltage value and in amiloride response ( reflecting sodium transport)		change from baseline (visit1) and placebo to miglustat instillation	No