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

NCT00945347 | Completed Phase 2

• 1 other identifier: MIG-99
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

Cystic fibrosis; miglustat; nasal instillation; nasal potential difference

Outcome Measures

Primary Outcomes (1)

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

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

Secondary Outcomes (1)

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

  change from baseline (visit1) and placebo to miglustat instillation

Study Arms (3)

Baseline

NO INTERVENTION

Visit 1

Miglustat

ACTIVE COMPARATOR

Nasal instillation of Miglustat (visit 2 or 3)

Drug: Miglustat

Placebo

PLACEBO COMPARATOR

Nasal instillation of placebo (visit 3 or 2)

Drug: Placebo

Interventions

Miglustat DRUG

Nasal instillation of miglustat

Miglustat

Placebo DRUG

Nasal instillation of placebo matching in appearance with the Miglustat instillation

Placebo

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (1)

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

Brussels, 1200, Belgium

Location

Related Publications (6)

• 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.

  PMID: 19299496 BACKGROUND

• 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. doi: 10.1016/j.febslet.2006.03.010. Epub 2006 Mar 10.

  PMID: 16546175 BACKGROUND

• Noel 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.

  PMID: 18309088 BACKGROUND

• 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.

  PMID: 19131642 BACKGROUND

• Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

  PMID: 37983082 DERIVED

• Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.

  PMID: 33331662 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

miglustat

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• 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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 23, 2009
• First Posted: July 24, 2009
• Study Start: July 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: June 1, 2011
• Last Updated: August 10, 2011

Record last verified: 2011-08

Locations

BE (1)