Lamotrigine as Treatment of Myotonia - a Phase 3 Randomized Controlled Trial Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- change from baseline in Myotonia Behavior Scale (MBS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Lamotrigine (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
change from baseline in Myotonia Behavior Scale (MBS)
时间窗: 8 weeks
Self evaluated Myotonia at the verified scale MBS. Participant evaluate myotonia for 4-7 days.
次要结局
- Change from baseline in evaluation of Myotonia(8 weeks)
- average in use of escape medicine(8 weeks)
- change from baseline in the SF-36 questionnaire(8 weeks)
研究者
Grete Andersen, MD
MD
Rigshospitalet, Denmark