A Safety and Tolerability Study of Mexiletine in Patients With Sporadic Amyotrophic Lateral Sclerosis (SALS)

Study Purpose:

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.

Study Status:

Not recruiting


Sporadic Amyotrophic Lateral Sclerosis

Study Type:


Type of Intervention:


Intervention Name:

Mexiletine, Placebo



Phase 2

Study Chair(s)/Principal Investigator(s):

Michael D Weiss, MD, University of Washington Medical School

Clinicaltrials.gov ID:


Neals Affiliated?


Coordinating Center Contact Information

Mass General

165 Cambridge St.
Boston, Massachusetts, 02109 United States

Full Study Summary:

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting primarily motor neurons, for which treatment designed to slow or arrest progression remains lacking. Mexiletine is a use-dependent sodium channel blocker that has been FDA-approved for decades for the treatment of cardiac arrhythmias and more recently to treat neuropathic pain in diabetic polyneuropathy. Mexiletine has been shown also to be protective of neurons following spinal cord, head injury, and cerebral ischemia, largely by blocking excitotoxicity. Based on previous studies, mexiletine appears to penetrate into the central nervous system at concentrations sufficient to confer significant protection. Recent unpublished studies in the laboratory of Dr. Robert Brown at the University of Massachusetts have also demonstrated that mexiletine ingestion in mice genetically engineered to express high levels of mutant cytosolic copper-zinc superoxide dismutase-1 (SOD1) transgene prolongs survival in these animals. As mexiletine already has FDA-approval as an anti-arrhythmic agent, much is known about the pharmacology and safety of this drug in non-ALS patients. We anticipate that by excluding subjects with a known history of cardiac disease and with the known neuroprotectant properties of this medication, mexiletine is a good choice for further study in an ALS clinical trial.

Study Sponsor:

University of Washington

Participant Duration:

Subjects will take study treatment for approximately 12 weeks. Subjects will have 5 in-person visits and 3 telephone calls during the study.

Estimated Enrollment:


Estimated Study Start Date:

06 / 30 / 2013

Estimated Study Completion Date:

08 / 01 / 2014

Posting Last Modified Date:

09 / 29 / 2021

Date Study Added to neals.org:

05 / 08 / 2013

July 1, 2015: ALS ACT will be funding further research

Minimum Age:

18 Years

Maximum Age:


Can participants use Riluzole?


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.

UCLA, Neuromuscular Research Center

Los Angeles, California 90095
United States

University of Iowa

Iowa City, Iowa 52242
United States

University of Kansas Medical Center

Kansas City, Kansas 66160
United States

Massachusetts General Hospital

Boston, Massachusetts 02114
United States

University of Massachusetts (Worcester) Memorial Medical Center

Worcester, Massachusetts 01655
United States

Washington University Medical School

Saint Louis, Missouri 63110
United States

SUNY Upstate Medical Center

Syracuse, New York 13210
United States

Penn State Hershey Medical Center

Hershey, Pennsylvania 17033
United States

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas 75390-8897
United States

University of Washington Medical Center

Seattle, Washington 98195
United States