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

Sponsor

Cliniques universitaires Saint-Luc- Université Catholique de Louvain (Other)

Overall Status

Completed

CT.gov ID

NCT00945347

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Miglustat Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, 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.

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

May 1, 2011

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

change in response to Chloride-free solution and isoproterenol ( reflecting chloride transport) [change from baseline ( visit 1) and placebo to miglustat instillation]

Secondary Outcome Measures

change in basal voltage value and in amiloride response ( reflecting sodium transport) [change from baseline (visit1) and placebo to miglustat instillation]

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	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)