Does a Nasal Instillation of Miglustat Normalize the Nasal Potential Difference in Cystic Fibrosis Patients ? - Full Text View

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:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Miglustat

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

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:

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
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 February 27, 2015