Mexiletine in Sporadic Amyotrophic Lateral Sclerosis
Condition: Sporadic Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Mexiletine; Placebo
Intervention MeSH terms: Mexiletine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SALS; Mexiletine; TMS; NCS

Summary:

      The purpose of this research study is to find out whether the drug mexiletine will be
      effective in lowering motor neuron electrical activity in the brains and nerves in the arms
      of people with ALS. The investigators will also determine if there are any signs that the
      drug may slow down the progression of ALS and reduce muscle cramps and muscle twitching. This
      will be determined through transcranial magnetic stimulation (TMS) and threshold tracking
      nerve conduction studies (TTNCS). In this trial, the participants will be taking either
      300mg/day of mexiletine, 600mg/day of mexiletine, or placebo (non-active study drug).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Sporadic ALS diagnosed as possible, laboratory-supported probable, probable, or
             definite ALS as defined by revised El Escorial criteria.

          2. Age 18 years or older.

          3. Symptom onset of weakness or spasticity due to ALS ≤ 60 months prior to Screening
             Visit.

          4. Slow vital capacity (SVC) measure ≥50% of predicted for gender, height, and age at the
             screening visit.

          5. Must be able to swallow capsules throughout the course of the study, according to Site
             Investigator judgment.

          6. Capable of providing informed consent and following trial procedures.

          7. For TMS: a resting motor threshold defined as 50% of pulses eliciting a motor evoked
             potential (MEP) of amplitude ≥ 50 µV.

          8. For TTNCS: median Compound Muscle Action Potential (CMAP) ≥ 1.5 mV.

          9. Subjects must not have taken riluzole for at least 30 days or be on a stable dose of
             riluzole for at least 30 days prior to the Screening Visit and continue on the stable
             dose throughout the course of the study (riluzole-naïve subjects are permitted in the
             study).

         10. Subjects must not have taken medication for muscle cramping such as cyclobenzaprine,
             baclofen, carisoprodol, or methocarbamol, for at least 30 days prior to screening or
             be on a stable dose for at least 60 days prior to screening.

         11. Geographic accessibility to the site.

         12. Women must not become pregnant for the duration of the study and must be willing to
             use two contraceptive therapies and have a negative pregnancy test throughout the
             course of the study.

         13. Use of medications known to affect the neurophysiology measures in the study must be
             scheduled, not as needed (pro re nata, PRN). A subject must have been on a fixed dose
             for 30 days prior to the Screening Visit, and there must be no reason to believe that
             a subsequent change would be necessary during the course of the study. These
             medications include: benzodiazepines, muscle relaxants, tricyclic antidepressants,
             selective serotonin reuptake inhibitors, non-selective serotonin reuptake inhibitors,
             hypnotics (including anti-histamines) and anti-cholinergics.

        Exclusion Criteria:

          1. Invasive ventilator dependence, such as tracheostomy.

          2. Creatinine level greater than 1.5 mg/dL at screening.

          3. Serum Glutamic-Oxaloacetic (SGOT/AST) / Serum Glutamic-Pyruvic (SGPT/ALT) greater than
             3 times the upper limit of normal at screening.

          4. History of known sensitivity or intolerability to mexiletine or lidocaine.

          5. Any history of either substance abuse within the past year, unstable psychiatric
             disease, cognitive impairment, or dementia.

          6. Clinically significant conduction abnormalities on electrocardiogram or a known
             history of cardiac arrhythmia.

          7. Known history of epilepsy.

          8. Known history of congestive heart failure (CHF) or history of myocardial infarction
             within the past 24 months.

          9. Use of mexiletine for 30 days prior to Screening Visit.

         10. Exposure to any other experimental agent (off-label use or investigational) including
             high dose creatine (>10 grams a day) within 30 days prior to Screening Visit.

         11. Metal in the head and neck region, cardiac pacemaker or brain stimulator, cochlear
             implants, implanted infusion device or personal history of epilepsy.

         12. Use of amiodarone, flecainide, duloxetine, tizanidine, or clozapine.

         13. Pregnant women or women currently breastfeeding.

         14. Placement of Diaphragm Pacing System (DPS) device < 60 days prior to Screening Visit.

         15. Planned DPS device implantation during study participation