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Lamotrigine as Treatment of Myotonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01939561
Recruitment Status : Completed
First Posted : September 11, 2013
Last Update Posted : April 25, 2016
Information provided by (Responsible Party):
Grete Andersen, MD, Rigshospitalet, Denmark

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Dystrophia Myotonica Type 1 Myotonia Congenita Paramyotonia Congenita Hyperkalemic Periodic Paralysis Potassium-Aggravated Myotonia Drug: Lamotrigine Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Lamotrigine as Treatment of Myotonia - a Phase 3 Randomized Controlled Trial Study
Study Start Date : November 2013
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015

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 Name: 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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

Other Outcome Measures:
  1. Lamotrigine blood concentration [ Time Frame: 8 weeks ]
    The blood concentration is compared with the effect of Lamotrigine on Myotonia

  2. change in creatin kinase level from baseline [ Time Frame: 8 weeks ]
    Levels are compared between treatment with placebo/Lamotrigine

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01939561

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Copenhagen Neuromuscular Center, department of Neurology, Rigshospitalet
Copenhagen, Denmark, DK-2100
Sponsors and Collaborators
Grete Andersen, MD
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Principal Investigator: Grete Andersen, MD Copenhagen Neuromuscular Center, Rigshospitalet, Denmark, Europe
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Responsible Party: Grete Andersen, MD, MD, Rigshospitalet, Denmark Identifier: NCT01939561    
Other Study ID Numbers: 2013-MY
2013-003309-24 ( EudraCT Number )
First Posted: September 11, 2013    Key Record Dates
Last Update Posted: April 25, 2016
Last Verified: April 2016
Keywords provided by Grete Andersen, MD, Rigshospitalet, Denmark:
Additional relevant MeSH terms:
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Myotonia Congenita
Myotonic Dystrophy
Myotonic Disorders
Paralysis, Hyperkalemic Periodic
Neurologic Manifestations
Nervous System Diseases
Neuromuscular Manifestations
Muscular Diseases
Musculoskeletal Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Muscular Dystrophies
Muscular Disorders, Atrophic
Paralyses, Familial Periodic
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents