Lamotrigine as Treatment of Myotonia

April 22, 2016 updated by: Grete Andersen, MD

Lamotrigine as Treatment of Myotonia - a Phase 3 Randomized Controlled Trial Study

Myotonia is a functional limiting symptom where the muscle stiffens on action leading to arrest of movement. Pharmacological treatment may make the difference between a physically restricted and a normal life. Today, patients with myotonia are treated with Mexiletine a medications resulting in adverse events up to 40 % and which very expensive and difficult to obtain.

Our clinic has, forced by the above problems related to Mexiletine, treated a few patients with the drug Lamotrigine with pronounced positive effect in all. Lamotrigine belongs to the same category of drugs as Mexiletine but has fewer and milder side effects. Based on the similarities of the 2 drugs in pharmacological action and the positive experiences investigators are convinced that Lamotrigine will show a positive effect if evaluated in a broader scale. Due to the advantages of Lamotrigine compared to Mexiletine investigators find it of outmost importance for patients that this drug is assessed formally to establish Lamotrigine as a treatment choice for myotonia. Investigators believe that this will potentially make a huge difference in life quality for persons with myotonia. Investigators aim at investigating the efficacy and tolerability of Lamotrigine in the treatment of myotonia in a randomized doublet blinded placebo controlled crossover study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In order to document that Lamotrigine is an effective treatment of myotonia investigators have chosen a 20-weeks double-blind randomized and placebo-controlled cross-over design.

Participants are randomized to receive either Lamotrigine or placebo in the first period (8 weeks) and the opposite in the second period (8 weeks). Between the two periods, a drug free period of minimum two weeks is included to ensure that participants receiving Lamotrigine in the first period, is no longer affected by the drug at the beginning of the second period.

Participants are schedules for six evaluations in the clinic, three in each period. At each evaluation, the degree of myotonia is determined and a blood sample is taken and analyzed, after study closure, to determine Lamotrigine level. Before each evaluation participants evaluate myotonia at home by the Myotonia Behavior Scale (MBS). Furthermore, participants had to complete the validated life quality questionnaire SF-36, before first period, in the drug free period, and after the second period.

Treatment: Participants are treated with escalating dosages (25/50/150/300 mg)of Lamotrigine/placebo once daily in two periods of eight weeks. Patients who prior to the study receive treatment, with drugs that can potentially influence myotonia, must stop the treatment during the study. Participants, who experience severe myotonia as defined by the MBS, are allowed to use escape medicine (Mexiletine) up until 60 hours before evaluation. Any use of Mexiletine will be noted and assessed as a part of the efficacy estimation. If Mexiletine is taken under 60 hours before evaluation blood concentration of Mexiletine is measured, to exclude data with blood concentration in the therapeutic level.

Disadvantage, Side effects and Safety: During the study participants cannot take their usual medications against myotonia. This can cause symptoms of myotonia, which can be a nuisance in the patient's everyday life.

Side effects of Lamotrigine treatment are usually mild. The most common are headaches and skin rash (2). All events and inconveniences will be registered and side effects will be reported to Health Authorities in accordance with current regulations.

The study will be stopped if there is a suspicion of a previously unknown side effect of Lamotrigine that can have an impact on the participant's life or feasibility.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • 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

  • Denmark
      • Copenhagen, Denmark, DK-2100
        • Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet

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

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinical myotonia: Myotonia affecting patients daily life, such as chewing function, handshake, initiation of walking and running, or dropping objects. Patients in antimyotonic treatment.
  • Gen-verified diagnosis: Myotonia Congenita, Paramyotonia Congenita, Potassium-aggravated Myotonia or Dystrophia Myotonica type 1.

Exclusion Criteria:

  • In treatment with medicines affecting the study results, estimated by investigators.
  • Participated in other drug-trials within 30 days prior to study start.
  • Known intolerance or allergy to Lamotrigine.
  • Significant renal or liver function, epilepsy, or long QT interval on the ECG.
  • Pregnancy and breast-feeding.
  • After the investigators discretion

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lamotrigine
Participants are taken oral tablets Lamotrigine once daily. The dosis is escalating every other weeks, from 25 mg - 50 mg - 150 mg- 300mg during the period of 8 weeks.
Drug: Lamotrigine
Other Names:
  • ATC-code: N03AX09
Placebo Comparator: Placebo
Participants are taken oral tablets placebo once daily. The dosis is escalating every other weeks, from 25 mg - 50 mg - 150 mg- 300 mg during the period of 8 weeks.
Drug: Placebo
Placebo is tablets identically with the Lamotrigine tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
change from baseline in Myotonia Behavior Scale (MBS)
Time Frame: 8 weeks
Self evaluated Myotonia at the verified scale MBS. Participant evaluate myotonia for 4-7 days.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in evaluation of Myotonia
Time Frame: 8 weeks
Myotonia is evaluated in the clinic by four tests. A eye-opening-test, a hand-grib-test, a TUG-test (time up and go) and a 14-step-stair-test. All test is evaluated in seconds.
8 weeks
average in use of escape medicine
Time Frame: 8 weeks
If a participants take escape medicine under the study it is recorded. Differences in use of escape medicine taken placebo/Lamotrigine is measured.
8 weeks
change from baseline in the SF-36 questionnaire
Time Frame: 8 weeks
SF-36 questionnaire is a standardized questionnaire measuring health. Participants completes the forms at home before first period, between tho two periods, and after the second period.
8 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lamotrigine blood concentration
Time Frame: 8 weeks
The blood concentration is compared with the effect of Lamotrigine on Myotonia
8 weeks
change in creatin kinase level from baseline
Time Frame: 8 weeks
Levels are compared between treatment with placebo/Lamotrigine
8 weeks

Collaborators and Investigators

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

Sponsor

Grete Andersen, MD

Investigators

  • Principal Investigator: Grete Andersen, MD, Copenhagen Neuromuscular Center, Rigshospitalet, Denmark, Europe

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

November 1, 2013

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

August 23, 2013

First Submitted That Met QC Criteria

September 5, 2013

First Posted (Estimate)

September 11, 2013

Study Record Updates

Last Update Posted (Estimate)

April 25, 2016

Last Update Submitted That Met QC Criteria

April 22, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013-MY
  • 2013-003309-24 (EudraCT Number)

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.

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