Mexiletine and Non Dystrophic Myotonias
Information source: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Non-dystrophic Myotonias; Paramyotonia Congenita; Myotonia Congenita
Intervention: Mexiletine (Drug); placebo (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Assistance Publique - Hôpitaux de Paris Official(s) and/or principal investigator(s): Bertrand Fontaine, MD, PhD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris Savine Vicart, MD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris
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:
1. study the safety and efficacy of mexiletine for the treatment of non-dystrophic
myotonias
2. validate electromyographic tests as a standardized outcome measure of myotonia
3. assess the reliability and validity of a new clinical rating scale for myotonia
Clinical Details
Official title: Efficacy and Safety of Mexiletine in Non-dystrophic Myotonias
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: score of stiffness severity on a self-assessment scale (100 mm VAS)
Secondary outcome: standardized EMG measures after repetitive short exercise test at cold and long exercise testchair 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)
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
1. 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.
2. 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:
1. provide data that justify recommendations for treatment strategies for myotonic
patients
2. provide data to justify AFSAPPS regulatory approval of mexiletine for treatment of
myotonia in order to guarantee the availability of the drug for patients
3. develop standardized diagnostic and treatment assessment for non-dystrophic myotonias
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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
Locations and Contacts
Groupe Hospitalier Pitié Salpetriere, Paris 75013, France
Additional Information
Starting date: June 2011
Last updated: January 12, 2015
|