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

NCT ID: NCT00945347

Last Updated: 2011-08-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-31

Study Completion Date

2011-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Baseline

Visit 1

Group Type NO_INTERVENTION

No interventions assigned to this group

Miglustat

Nasal instillation of Miglustat (visit 2 or 3)

Group Type ACTIVE_COMPARATOR

Miglustat

Intervention Type DRUG

Nasal instillation of miglustat

Placebo

Nasal instillation of placebo (visit 3 or 2)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Nasal instillation of placebo matching in appearance with the Miglustat instillation

Interventions

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Miglustat

Nasal instillation of miglustat

Intervention Type DRUG

Placebo

Nasal instillation of placebo matching in appearance with the Miglustat instillation

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role lead

Responsible Party

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Cliniques universitaires Saint Luc (Université Catholique de Louvain)

Principal Investigators

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Patrick LEBECQUE, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cliniques Universitaires St Luc (Université Catholique de Louvain )

Teresinha LEAL, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cliniques Universitaires St. Luc ( Université Catholique de Louvain)

Locations

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

Brussels, , Belgium

Site Status

Countries

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Belgium

References

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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.

Reference Type BACKGROUND
PMID: 19299496 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16546175 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18309088 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19131642 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37983082 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33331662 (View on PubMed)

Other Identifiers

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MIG-99

Identifier Type: -

Identifier Source: org_study_id

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