Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (SALS)
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: 75.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SALS; Mexiletine; Safety

Summary:

      The purpose of this research is to find out if mexiletine is safe and effective in people
      with Amyotrophic Lateral Sclerosis (ALS). In this trial, participants will be taking either
      300 milligrams per day of mexiletine, 900 milligrams per day of mexiletine or placebo
      (non-active study drug). The safety and efficacy of these doses will be compared to see if
      one dose is better than the other.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Sporadic Amyotrophic Lateral Sclerosis (SALS) diagnosed as possible,
             laboratory-supported probable, probable, or definite ALS as defined by revised El
             Escorial criteria.

          -  Age 18 years or older.

          -  Disease duration ≤ 36 months from ALS symptom onset.

          -  Capable of providing informed consent and following trial procedures.

          -  Subjects must not have taken riluzole for at least 30 days or be on a 50 milligrams
             twice daily dose of riluzole for at least 60 days prior to randomization
             (riluzole-naïve subjects are permitted in the study).

          -  Subjects must not have taken medication for muscle cramping such as cyclobenzaprine,
             baclofen, carisoprodol, or methocarbamol, for at least 30 days prior to randomization
             or be on a stable dose for at least 60 days prior to randomization.

          -  Geographic accessibility to the site.

          -  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.

          -  Slow vital capacity (SVC) measure greater than or equal to 50% of predicted for
             gender, height, and age at the screening visit.

          -  Subjects medically able to undergo lumbar puncture (LP) as determined by the
             investigator (for example, no bleeding disorder, allergy to local anesthetics, a skin
             infection at or near the LP site, or evidence of high intracranial pressure).

          -  Must be able to swallow capsules throughout the course of the study, according to
             Principal Investigator (PI) judgment.

          -  Must have a caregiver assist with dispensing the study drug.

        Exclusion Criteria:

          -  Invasive ventilator dependence, such as tracheostomy.

          -  Creatinine level greater than 1.5 milligram/deciliter.

          -  Serum glutamic oxaloacetic transaminase or (aspartate transaminase) / serum glutamic
             pyruvic transaminase (alanine aminotransferase) greater than 3 times the upper limit
             of normal at screening.

          -  History of known sensitivity or intolerability to mexiletine or lidocaine.

          -  Any history of either substance abuse within the past year, unstable psychiatric
             disease, cognitive impairment, or dementia.

          -  Clinically significant conduction abnormalities on electrocardiogram or a known
             history of cardiac arrhythmia.

          -  Known history of epilepsy.

          -  Known history of congestive heart failure (CHF) or history of myocardial infarction
             within the past 24 months.

          -  Use of mexiletine for 60 days prior to Baseline Visit.

          -  Exposure to any other experimental agent (off-label use or investigational) including
             high dose creatine (greater than 10 grams a day) within 30 days prior to Baseline
             Visit.

          -  Use of amiodarone, flecainide, duloxetine, tizanidine, or clozapine.

          -  Pregnant women or women currently breastfeeding.

          -  Placement of Diaphragm Pacing System (DPS) device less than 60 days prior to Baseline
             Visit.

          -  Planned DPS device implantation after Baseline Visit.