Mexiletine for the Treatment of Muscle Cramps in ALS
Condition: Muscle Cramps in Amyotrophic Lateral Sclerosis
MeSH terms: Muscle Cramp; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Spasm; Sclerosis
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine if mexiletine is effective for the treatment of
      muscle cramps in Amyotrophic Lateral Sclerosis (ALS).
    

Detailed description: 
      Background:

      Many ALS patients suffer from painful muscle cramps, but unfortunately we do not have any
      medication proven to help muscle cramps in ALS. Reducing the pain caused by cramps - which
      can be debilitating - could help people living with ALS.

      Muscle cramps are sudden, painful, and involuntary contractions of a muscle. They are caused
      by nerve dysfunction. When we examine nerves and muscles electrically, we see cramps as
      bursts of high-frequency (up to150 Hz) firing of the motor nerve cells. Cramps in ALS are
      believed to be the result of an increase of persistent sodium currents in the sick lower
      motor nerve cells.

      A medication called Quinine was for many years the commonly used drug for controlling cramps
      in ALS, but the FDA has advised against its use for cramps because of its potential risks
      (e.g., death). Today there is no agreement on how to treat cramps in the ALS. The American
      Academy of Neurology recently encouraged further studies of the treatment of muscle cramps
      and suggested lidocaine as one of a few drugs of special interest.

      Mexiletine:

      Mexiletine is a medication closely related to lidocaine that can be taken by mouth (instead
      of being injected). Mexiletine stops the type of sodium currents that are thought to cause
      muscle cramps. Mexiletine is a relatively older medication that has been extensively studied
      in humans. It has been shown to reduce the electrical measures of muscle cramps for other
      disease conditions. For example, in patients with another severe nerve disease -
      Machado-Joseph disease (SCA3) - mexiletine treatment led to a decrease in the average number
      of muscle cramps from 24 to 3 cramps per month.. The safety profile of mexiletine is good,
      with the most frequent side effects being nausea or other abdominal symptoms. These side
      effects are rare at the doses (300 mg/day) used in this study. In patients with normal heart
      function, mexiletine has a minimal effect on heart rhythm. In previous clinical trials, no
      subject developed any serious heart rate problem.

      Experimental Plan:

      Using multiple sites within the State of California we will quickly enroll a small number
      (N=30) of ALS patients with severe muscle cramps. The study is a double-blinded, placebo
      controlled (i.e., the investigator and the participant does not know if the pills contain
      mexiletine or placebo), crossover (all subjects receive two weeks of mexiletine and two weeks
      of placebo) study.

      After a one week run in, participants will be evaluated on their ability to fill out the
      cramp diary. Participants who filled out their diary will be randomly assigned to either
      mexiletine or placebo for their first two weeks. For the first three days of each 2-week
      period, one 150mg capsule will be taken at bed time. For day 4 to 14 one capsule twice per
      day will be taken. Each treatment period will be 2 weeks with an intervening 1 week washout
      period - for a total study length of 6 weeks. Safety will be monitored with liver function
      studies and EKG's.
    

Intervention name(s): Mexiletine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Sodium channel blocker; Placebo
Other intervention name(s): Mexetil; Sugar pill
Intervention MeSH terms: Mexiletine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Muscle cramps; Cramp; ALS; Amyotrophic Lateral Sclerosis; Lou Gehrig's disease; Motor Neuron Disease; MND