Trial record 1 of 2 for:    HYPERKALEMIC PERIODIC PARALYSIS
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Lamotrigine as Treatment of Myotonia

This study is currently recruiting participants.
Verified November 2013 by Rigshospitalet, Denmark
Sponsor:
Information provided by (Responsible Party):
Grete Andersen, MD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01939561
First received: August 23, 2013
Last updated: November 11, 2013
Last verified: November 2013
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Lamotrigine as Treatment of Myotonia - a Phase 3 Randomized Controlled Trial Study

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • change from baseline in Myotonia Behavior Scale (MBS) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Self evaluated Myotonia at the verified scale MBS. Participant evaluate myotonia for 4-7 days.


Secondary Outcome Measures:
  • Change from baseline in evaluation of Myotonia [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.

  • average in use of escape medicine [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    If a participants take escape medicine under the study it is recorded. Differences in use of escape medicine taken placebo/Lamotrigine is measured.

  • change from baseline in the SF-36 questionnaire [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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:
  • Lamotrigine blood concentration [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The blood concentration is compared with the effect of Lamotrigine on Myotonia

  • change in creatin kinase level from baseline [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Levels are compared between treatment with placebo/Lamotrigine


Estimated Enrollment: 36
Study Start Date: November 2013
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01939561

Contacts
Contact: Grete Andersen, MD 004535456135 grete.andersen@regionh.dk

Locations
Denmark
Neuromuscular reasearch unit, department of Neurology, Rigshospitalet Recruiting
Copenhagen, Denmark, DK-2100
Contact: Grete Andersen, MD    004535456135    grete.andersen@regionh.dk   
Principal Investigator: Grete Andersen, MD         
Sub-Investigator: Gitte H Pedersen, BA         
Sponsors and Collaborators
Grete Andersen, MD
Investigators
Principal Investigator: Grete Andersen, MD Neuromuscular research unit, Rigshospitalet, Copenhagen, Denmark
  More Information

No publications provided

Responsible Party: Grete Andersen, MD, MD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01939561     History of Changes
Other Study ID Numbers: 2013-MY, 2013-003309-24
Study First Received: August 23, 2013
Last Updated: November 11, 2013
Health Authority: Denmark: Danish Health and Medicines Authority
Denmark: Danish Dataprotection Agency
Denmark: Ethics Committee

Keywords provided by Rigshospitalet, Denmark:
Myotonia
Lamotrigine
RCT
treatment

Additional relevant MeSH terms:
Paralyses, Familial Periodic
Paralysis, Hyperkalemic Periodic
Paralysis
Myotonia
Myotonic Dystrophy
Myotonia Congenita
Myotonic Disorders
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Lamotrigine
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Anticonvulsants

ClinicalTrials.gov processed this record on April 17, 2014