Effect of Miglustat on the Nasal Potential Difference in Patients With Cystic Fibrosis Homozygous for the F508del Mutation (MIGLUSTAT-CF)

November 17, 2025 updated by: Assistance Publique - Hôpitaux de Paris

Single Center, Double-blind, Randomized, Placebo-controlled, Two-period/Two-treatment Crossover, Proof-of-mechanism Study Investigating the Effect of Miglustat on the Nasal Potential Difference in Adult Patients With Cystic Fibrosis Homozygous for the F508del Mutation

The purpose of this study is to demonstrate that Miglustat restores the function of the cystic fibrosis transmembrane conductance regulator (CFTR) in adult patients with cystic fibrosis homozygous for the F508del mutation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The aims of this study are:

  1. To determine whether Miglustat can restore the function of the CFTR protein in adult patients with cystic fibrosis homozygous for the F508del mutation
  2. To evaluate the safety, tolerability and pharmacokinetics of Miglustat in adult patients with cystic fibrosis homozygous for the F508del mutation.
  3. To investigate pharmacokinetic-pharmacodynamic of Miglustat in adult patients with cystic fibrosis homozygous for the F508del mutation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75014
        • Assistance publique-Hôpitaux de Paris, Hôpital Cochin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Inclusion criteria at screening visit (Visit 1):

  • Aged 18 years and older
  • Male or female

  • Women of childbearing potential must:

    • have a negative serum pregnancy test at Visit 1
    • agree to use from Visit 1 until 3 months after the last study drug intake a reliable method of contraception
  • Male patients accepting for the duration of the study and for 3 months thereafter to use a condom
  • Homozygous for the F508del mutation as confirmed by genetic testing
  • Sweat chloride ≥ 60 mmol/L
  • Basal nasal potential difference (NPD) ≤ -30.0 mV (equal to or more electrically negative than -30.0 mV) and total chloride secretion (TCS) ≥ - 5.0 mV for at least one nostril. However, if it is possible to analyze both nostrils, the total chloride secretion (TCS) is to be ≥ - 5.0 mV (equal to or more electrically positive than - 5.0 mV) in both nostrils.
  • FEV1 ≥ 25% of predicted
  • Able to comply with all protocol requirements
  • Signed informed consent prior to any study-mandated procedure

Inclusion criteria at randomization visit (Visit 2):

  • Women of child-bearing potential must have a negative urine pregnancy test
  • Basal nasal potential difference (NPD) ≤ - 30.0 mV (equal to or more electrically negative than - 30.0 mV) and total chloride secretion (TCS) ≥ - 5.0 mV for at least one nostril. However, if it is possible to analyze both nostrils, the total chloride secretion (TCS) is to be ≥ - 5.0 mV (equal to or more electrically positive than - 5.0 mV) in both nostrils.

Exclusion Criteria:

  • Any condition prohibiting the correct measurement of the NPD such as upper respiratory tract infection
  • Acute upper or lower respiratory tract infection requiring antibiotic intervention within 2 weeks of screening
  • Lung transplant recipient or patient on a lung transplant waiting list
  • Any modification in regular treatments (new treatment initiated or discontinued treatment) or modification in dosing within 2 weeks prior to start of Period 1
  • Moderate/Severe renal impairment (creatinine clearance < 70 mL/min as per Cockroft and Gault)
  • Systemic corticosteroids (> 10 mg/day prednisone or equivalent) within 14 days prior to screening and up to start of study
  • Women who are breast-feeding, pregnant, or who plan to become pregnant during the course of the study
  • History of significant lactose intolerance
  • Presence of clinically significant diarrhoea (> 3 liquid stools per day for > 7 days) without definable cause within one month prior to screening
  • Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
  • Active or passive smoking
  • Hypersensitivity to Miglustat or any excipients
  • Planned treatment or treatment with another investigational drug or therapy (e.g., gene therapy) within one month prior to randomization
  • Known concomitant life-threatening disease with a life expectancy < 12 months
  • Indication against Isuprel® (Isoproterenol) including heart diseases.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Miglustat then placebo
10 patients will received Miglustat then the placebo
Drug: Miglustat ; placebo
For this 2 x 2 (2 periods /2 treatments) crossover design each patient will receive Miglustat during the first period (2 weeks), following by a wash out period(14 days (up to 4 weeks)), then Placebo during the second period (2 weeks). 30 days follow-up will be carried out after end-of-treatment of the second period.
Experimental: Placebo then Miglustat
10 patients will received Placebo then Miglustat
Drug: Placebo ; Miglustat
For this 2 x 2 (2 periods /2 treatments) crossover design each patient will receive Placebo during the first period (2 weeks), following by wash out period (14 days (up to 4 weeks)), then Miglustat during the second period (2 weeks). 30 days follow-up will be carried out after end of treatment of the second period.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean TCS in mV
Time Frame: day 1
TCS (Total Chloride Secretion) is the sum of responses in nasal potential difference (NPD) calculated as the mean of the right and left nostril measurements for each patient
day 1
Mean TCS in mV
Time Frame: Day 14
TCS (Total Chloride Secretion) is the sum of responses in nasal potential difference (NPD) calculated as the mean of the right and left nostril measurements for each patient
Day 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
TCS difference in mV
Time Frame: day 1
TCS difference is calculated as the change in measurements of TCS for the right and left nostrils independently for each patient.
day 1
TCS difference in mV
Time Frame: Day 14
TCS difference is calculated as the change in measurements of TCS for the right and left nostrils independently for each patient.
Day 14
Percentage of patients with a TCS response to treatment ≤ - 5 mV
Time Frame: day 1
The percentage of patients with a TCS response to treatment defined as a difference in TCS from baseline to end-of-treatment ≤ -5mV
day 1
Percentage of patients with a TCS response to treatment ≤ - 5 mV
Time Frame: day 14
The percentage of patients with a TCS response to treatment defined as a difference in TCS from baseline to end-of-treatment ≤ -5mV
day 14
Percentage of patients with a TCS at end-of-treatment ≤ - 5 mV
Time Frame: day 1
The percentage of patients with a TCS response at end-of-treatment ≤ -5mV
day 1
Percentage of patients with a TCS at end-of-treatment ≤ - 5 mV
Time Frame: day 14
The percentage of patients with a TCS response at end-of-treatment ≤ -5mV
day 14
Change of basal NPD in mV
Time Frame: day 1
Basal NPD at end-of-treatment minus basal NPD at baseline
day 1
Change of basal NPD in mV
Time Frame: day 14
Basal NPD at end-of-treatment minus basal NPD at baseline
day 14
Change of the response in NPD after superfusion with amiloride
Time Frame: day 1
NPD after superfusion with amiloride at end-of-treatment minus NPD after superfusion with amiloride at baseline
day 1
Change of the response in NPD after superfusion with amiloride
Time Frame: day 14
NPD after superfusion with amiloride at end-of-treatment minus NPD after superfusion with amiloride at baseline
day 14
Change of the response in NPD after superfusion with a chloride-free buffer in the presence of amiloride
Time Frame: day 1
NPD after superfusion with a chloride-free buffer in the presence of amiloride at end-of-treatment minus NPD after superfusion with a chloride-free buffer in the presence of amiloride at baseline
day 1
Change of the response in NPD after superfusion with a chloride-free buffer in the presence of amiloride
Time Frame: day 14
NPD after superfusion with a chloride-free buffer in the presence of amiloride at end-of-treatment minus NPD after superfusion with a chloride-free buffer in the presence of amiloride at baseline
day 14
Wilschanski's index change
Time Frame: day 1
Wilschanski's index is defined as (exposant(response to Chloride-free and isoproterenol/response amiloride)): Wilschanski's index at end-of-treatment minus Wilschanski's at baseline
day 1
Wilschanski's index change
Time Frame: day 14
Wilschanski's index is defined as (exposant(response to Chloride-free and isoproterenol/response amiloride)): Wilschanski's index at end-of-treatment minus Wilschanski's at baseline
day 14
Sweat chloride concentration in mmol/L
Time Frame: day 1
Sweat chloride concentration at end-of-treatment minus sweat chloride concentration at baseline
day 1
Sweat chloride concentration in mmol/L
Time Frame: day 14
Sweat chloride concentration at end-of-treatment minus sweat chloride concentration at baseline
day 14
FEV1 (in % of predicted)
Time Frame: day 1
Pulmonary function FEV1: mean Forced expiry volume in 1 second. FEV1 at end-of-treatment minus FEV1 at baseline
day 1
FEV1 (in % of predicted)
Time Frame: day 14
Pulmonary function FEV1: mean Forced expiry volume in 1 second. FEV1 at end-of-treatment minus FEV1 at baseline
day 14
Change in electrochemical skin conductance
Time Frame: day 1
Electrochemical skin conductance at end-of-treatment minus electrochemical skin conductance at baseline
day 1
Change in electrochemical skin conductance
Time Frame: day 14
Electrochemical skin conductance at end-of-treatment minus electrochemical skin conductance at baseline
day 14
Number of cells expressing CFTR at the cell membrane (in %percentage)
Time Frame: day 14
Percentage of nasal cells expressing CFTR at the cell membrane as assessed by immunochemistry and confocal microscopy
day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Actelion
URC-CIC Paris Descartes Necker Cochin
CRCM (Centres de Ressources et de Compétences de la Mucoviscidose)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Isabelle FAJAC, MD, PhD., Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 17, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 3, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 3, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 10, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 25, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 20, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P120703
  • 2013-000497-29 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings