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Mexiletine and Non Dystrophic Myotonias (MYOMEX)

Primary Purpose

Non-dystrophic Myotonias, Paramyotonia Congenita, Myotonia Congenita

Status

Completed

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Mexiletine

placebo

About this trial

This is an interventional treatment trial for Non-dystrophic Myotonias focused on measuring non-dystrophic myotonias, paramyotonia congenita, myotonia congenita, Mexiletine, Randomized clinical trial

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria :

Genetically definite MC and PC.
Male and female participants, age between 18 and 65 who are able to comply with the study conditions.
Participants who experience myotonic symptoms severe enough to justify treatment.

The severity will be evaluated on:

Clinical criteria: myotonia is considered as severe if it involves at least two segments (upper limb, lower limb or face)
Disabling criteria: myotonia is considered severe if patients notice impacts on at least 3 of the 7 daily activities listed in the disabling section of the clinical myotonia scale (Annex 2).

Thus, patients who experience myotonic symptoms severe enough to justify treatment are those with myotonia that involves at least two segments and that have an impact on at least 3 daily activities.

Participants who are drug naive or those who receiving mexiletine at Effective dosage and agreeing to stop treatment at least four days before inclusion .
Pregnancy: Women: non-childbearing potential (i.e., postmenopausal or Surgically sterile) or must use a medically accepted contraceptive regimen; a pregnancy test will ensure that they are not pregnant.
Normal cardiac exam performed by a cardiologist including EKG, and Cardiac ultrasound (if not done within 3 months before trial).

Exclusion criteria :

Intercurrent event which could interfere with the muscle function (infection,trauma, fracture, …)
Coincidental renal, hepatic, respiratory, thyroid, other neuromuscular disease or heart disease that will contraindicate mexiletine or interfere with clinical evaluation.
Use of any of the following medications that can interfere with muscle function :diuretics, anti epileptics (sodium channel blockers), antiarrhythmics, corticosteroids, beta-blockers,
Allergy to mexiletine

Sites / Locations

Groupe Hospitalier Pitié Salpetriere

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm Description

Mexiletine / Placebo

Placebo / Mexiletine

Outcomes

Primary Outcome Measures

score of stiffness severity on a self-assessment scale (100 mm VAS)

Secondary Outcome Measures

standardized EMG measures after repetitive short exercise test at cold and long exercise test

chair test: time needed to stand up from a chair, walk around it and sit down again

severity and disability scale of myotonia to be validated

quality of life scale (INQOL)

CGI efficacy (Clinical Global Impression- Efficacy index)

Full Information

NCT ID

NCT02336477

First Posted

January 8, 2015

Last Updated

January 12, 2015

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT02336477

Brief Title

Mexiletine and Non Dystrophic Myotonias

Acronym

MYOMEX

Official Title

Efficacy and Safety of Mexiletine in Non-dystrophic Myotonias

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Completed

Study Start Date

June 2011 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Treatment strategies in non-dystrophic myotonias are based on selective case reports, clinical experience and theoretical benefit. Presently, the most promising antimyotonic medication is mexiletine (MEX) but its manufacturing was stopped. The proposed randomized, double-blind, placebo-controlled, crossover trial is designed to: study the safety and efficacy of mexiletine for the treatment of non-dystrophic myotonias validate electromyographic tests as a standardized outcome measure of myotonia assess the reliability and validity of a new clinical rating scale for myotonia

Detailed Description

A. Specific aims Treatment strategies in non-dystrophic myotonias are based on selective case reports, clinical experience and theoretical benefit. Presently, the most promising antimyotonic medication is mexiletine (MEX) but its manufacturing was stopped. The proposed randomized, double-blind, placebo-controlled, crossover with wash-out trial is designed to: study the safety and efficacy of mexiletine for the treatment of non-dystrophic myotonias validate electromyographic tests as a standardized outcome measure of myotonia assess the reliability and validity of a new clinical rating scale for myotonia B. Research design Because of their differing phenotypes, 12 Paramyotonia Congenita and 12 Myotonia Congenita subjects will be enrolled in a stratified trial C. Outcome variables primary outcome variable: the score of stiffness severity on a self-assessment scale (100 mm VAS) measured at baseline, at the end of phase I and phase II. secondary outcome measures: of efficacy: standardized EMG measures after repetitive short exercise test at cold and long exercise test chair test: time needed to stand up from a chair, walk around it and sit down again severity and disability scale of myotonia to be validated) quality of life scale (INQOL) rate of drop-outs of safety: adverse event frequency and severity EKG D. Perspectives It is anticipated that the trial will: provide data that justify recommendations for treatment strategies for myotonic patients provide data to justify AFSAPPS regulatory approval of mexiletine for treatment of myotonia in order to guarantee the availability of the drug for patients develop standardized diagnostic and treatment assessment for non-dystrophic myotonias

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-dystrophic Myotonias, Paramyotonia Congenita, Myotonia Congenita

Keywords

non-dystrophic myotonias, paramyotonia congenita, myotonia congenita, Mexiletine, Randomized clinical trial

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Mexiletine / Placebo

Arm Title

Arm Type

Experimental

Arm Description

Placebo / Mexiletine

Intervention Type

Drug

Intervention Name(s)

Mexiletine

Intervention Description

Blisters of 10 capsules of 200 mg mexiletine hydrochloride. Patients will receive gradual dose of the treatment as it would be done in clinical practice. Mexiletine will be started at 200 mg / day (1 capsule to be taken at the beginning of the meal) and will be increased by 200mg every 3 days to reach a maximum of 600mg / day in 3 taken in 1 week. The duration of each treatment period is 18 days minimum (maximum 22 days).

Intervention Type

Drug

Intervention Name(s)

placebo

Primary Outcome Measure Information:

Title

score of stiffness severity on a self-assessment scale (100 mm VAS)

Time Frame

18 days

Secondary Outcome Measure Information:

Title

standardized EMG measures after repetitive short exercise test at cold and long exercise test

Time Frame

18 days

Title

chair test: time needed to stand up from a chair, walk around it and sit down again

Time Frame

18 days

Title

severity and disability scale of myotonia to be validated

Time Frame

18 days

Title

quality of life scale (INQOL)

Time Frame

18 days

Title

CGI efficacy (Clinical Global Impression- Efficacy index)

Time Frame

18 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria : Genetically definite MC and PC. Male and female participants, age between 18 and 65 who are able to comply with the study conditions. Participants who experience myotonic symptoms severe enough to justify treatment. The severity will be evaluated on: Clinical criteria: myotonia is considered as severe if it involves at least two segments (upper limb, lower limb or face) Disabling criteria: myotonia is considered severe if patients notice impacts on at least 3 of the 7 daily activities listed in the disabling section of the clinical myotonia scale (Annex 2). Thus, patients who experience myotonic symptoms severe enough to justify treatment are those with myotonia that involves at least two segments and that have an impact on at least 3 daily activities. Participants who are drug naive or those who receiving mexiletine at Effective dosage and agreeing to stop treatment at least four days before inclusion . Pregnancy: Women: non-childbearing potential (i.e., postmenopausal or Surgically sterile) or must use a medically accepted contraceptive regimen; a pregnancy test will ensure that they are not pregnant. Normal cardiac exam performed by a cardiologist including EKG, and Cardiac ultrasound (if not done within 3 months before trial). Exclusion criteria : Intercurrent event which could interfere with the muscle function (infection,trauma, fracture, …) Coincidental renal, hepatic, respiratory, thyroid, other neuromuscular disease or heart disease that will contraindicate mexiletine or interfere with clinical evaluation. Use of any of the following medications that can interfere with muscle function :diuretics, anti epileptics (sodium channel blockers), antiarrhythmics, corticosteroids, beta-blockers, Allergy to mexiletine

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bertrand Fontaine, MD, PhD

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Savine Vicart, MD

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Groupe Hospitalier Pitié Salpetriere

City

Paris

ZIP/Postal Code

75013

Country

France

12. IPD Sharing Statement

Learn more about this trial

Mexiletine and Non Dystrophic Myotonias

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