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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Baseline | No Intervention | Visit 1 | |
| Miglustat | Active Comparator | Nasal instillation of Miglustat (visit 2 or 3) |
|
| Placebo | Placebo Comparator | Nasal instillation of placebo (visit 3 or 2) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Miglustat | Drug | Nasal instillation of miglustat |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| change in response to Chloride-free solution and isoproterenol ( reflecting chloride transport) | change from baseline ( visit 1) and placebo to miglustat instillation |
| Measure | Description | Time Frame |
|---|---|---|
| change in basal voltage value and in amiloride response ( reflecting sodium transport) | change from baseline (visit1) and placebo to miglustat instillation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cliniques Universitaires St Luc (Université Catholique de Louvain) 10 avenue Hippocrate | Brussels | 1200 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19299496 | Background | 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. | |
| 16546175 | Background |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C059896 | miglustat |
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| Drug |
Nasal instillation of placebo matching in appearance with the Miglustat instillation |
|
| 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. |
| 18309088 | 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. |
| 19131642 | 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. |
| 37983082 | Derived | 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. |
| 33331662 | 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. |
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |