Mexiletine and Non Dystrophic Myotonias

NCT02336477 | Completed Phase 3 DMC

• 1 other identifier: P091101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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:

1. 1.study the safety and efficacy of mexiletine for the treatment of non-dystrophic myotonias
2. 2.validate electromyographic tests as a standardized outcome measure of myotonia
3. 3.assess the reliability and validity of a new clinical rating scale for myotonia

Conditions

Non-dystrophic Myotonias; Paramyotonia Congenita; Myotonia Congenita

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  18 days

Secondary Outcomes (5)

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

  18 days

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

  18 days

• severity and disability scale of myotonia to be validated

  18 days

• quality of life scale (INQOL)

  18 days

• CGI efficacy (Clinical Global Impression- Efficacy index)

  18 days

Study Arms (2)

1

EXPERIMENTAL

Mexiletine / Placebo

Drug: Mexiletine; Drug: placebo

2

EXPERIMENTAL

Placebo / Mexiletine

Drug: Mexiletine; Drug: placebo

Interventions

Mexiletine DRUG

* 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).

1; 2

placebo DRUG

1; 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Groupe Hospitalier Pitié Salpetriere

Paris, 75013, France

Location

MeSH Terms

Conditions

Myotonic Disorders; Myotonia Congenita

Interventions

Mexiletine

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Phenyl Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Bertrand Fontaine, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Savine Vicart, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2015
• First Posted: January 13, 2015
• Study Start: June 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 13, 2015

Record last verified: 2015-01

Locations

FR (1)