Effect of Mexiletine on Cortical Hyperexcitability in Sporadic Amyotrophic Lateral Sclerosis (SALS)

Full Study 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

  Gender:

  Female, Male

  Minimum Age:

  18

  Maximum Age:

  N/A

  Min Vital Capacity (% predicted normal):

  50

  Time since Symptom Onset:

  >36 months

  Time since Diagnosis:

  Can participants use Riluzole?

  Yes

  
  

  Inclusion Criteria:
  Sporadic ALS diagnosed as possible, laboratory-supported probable, probable, or definite ALS as defined by revised El Escorial criteria.
  Age 18 years or older.
  Symptom onset of weakness or spasticity due to ALS ≤ 60 months prior to Screening Visit.
  Slow vital capacity (SVC) measure ≥50% of predicted for gender, height, and age at the screening visit.
  Must be able to swallow capsules throughout the course of the study, according to Site Investigator judgment.
  Capable of providing informed consent and following trial procedures.
  For TMS: a resting motor threshold defined as 50% of pulses eliciting a motor evoked potential (MEP) of amplitude ≥ 50 µV.
  For TTNCS: median Compound Muscle Action Potential (CMAP) ≥ 1.5 mV.
  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).
  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.
  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.
  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:
  Invasive ventilator dependence, such as tracheostomy.
  Creatinine level greater than 1.5 mg/dL at screening.
  Serum Glutamic-Oxaloacetic (SGOT/AST) / Serum Glutamic-Pyruvic (SGPT/ALT) 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 30 days prior to Screening Visit.
  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.
  Metal in the head and neck region, cardiac pacemaker or brain stimulator, cochlear implants, implanted infusion device or personal history of epilepsy.
  Use of amiodarone, flecainide, duloxetine, tizanidine, or clozapine.
  Pregnant women or women currently breastfeeding.
  Placement of Diaphragm Pacing System (DPS) device < 60 days prior to Screening Visit.
  Planned DPS device implantation during study participation

• Site Contact Information

  Barrow Neurological Institute
  Nicole Turcotte / .(JavaScript must be enabled to view this email address) / 602-406-4775
  240 W. Thomas Rd.
  Phoenix, Arizona 85013
  United States

  University of California, Irvine
  Veena Mathew / .(JavaScript must be enabled to view this email address) / 714-456-2864
  200 S Manchester Ave
  Orange, California 92868
  United States

  Augusta University, Georgia Regents
  Kristy Bouchard / .(JavaScript must be enabled to view this email address) / 706-721-2681
  1120 15th Street
  Augusta, Georgia 30912
  United States

  Beth Israel Deaconess Medical Center
  Hilda Gutierrez / .(JavaScript must be enabled to view this email address) / 617-667-3086
  330 Brookline Ave.
  Boston, Massachusetts 02215
  United States

  University of Michigan
  Jayna Duell, BSN, RN / .(JavaScript must be enabled to view this email address) / 734-763-9037
  1500 E. Medical Center Drive
  Ann Arbor, Michigan 48109
  United States

  Columbia University Medical Center
  Jess Singleton / .(JavaScript must be enabled to view this email address) / 212-305-7221
  622 West 168th Street,
  New York, New York 10032
  United States

  Penn State
  Jen Crossen / .(JavaScript must be enabled to view this email address) / 717-531-0003 ext 280842
  Hershey, Pennsylvania 17033
  United States

  University of Pittsburgh
  Danielle Rowlands / .(JavaScript must be enabled to view this email address) / 412-864-2873
  200 Lothrop Street
  Pittsburgh, Pennsylvania 15213
  United States

  Medical University of South Carolina
  Michele DeCandio, RN, OCN, CCRP / .(JavaScript must be enabled to view this email address) / 843-792-9016
  Charleston, South Carolina 29425
  United States

  University of Washington
  Laura Sissons-Ross / .(JavaScript must be enabled to view this email address) / 206-543-0081
  1959 NE Pacific St.
  Seattle, Washington 98195
  United States