A Safety and Tolerability Study of Mexiletine in Patients with Sporadic ALS (SALS)

Study Purpose:

The purpose of this study is to determine if mexiletine is safe and tolerable in volunteers with sporadic ALS (SALS).

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Closed

Phase:

Phase II

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

Michael Weiss, MD (University of Washington School of Medicine, Seattle, WA)
Merit Cudkowicz, MD, MSc (Massachusetts General Hospital)

Clinicaltrials.gov ID (11 digit #):

NCT01849770

Neals Affiliated?

Yes

Coordinating Center Contact Information

Mass General
Daniela Grasso / .(JavaScript must be enabled to view this email address) / 617-726-0842
.(JavaScript must be enabled to view this email address) 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 to be protective of neurons following spinal cord, head injury, and cerebral ischemia, largely by blocking excitotoxicity. Recent unpublished studies have shown that mexiletine prolongs survival in animal models of ALS. Since mexiletine has not been rigorously evaluated in ALS populations, a clinical trial has been designed to scientifically determine the safety and tolerability, as well as the effect of mexiletine on ALS patients.

Approximately 60 eligible subjects with sporadic ALS will be recruited from multiple centers in the US. Subjects will be treated for 12 weeks with either mexiletine (300 mg/day or 900 mg/day) or placebo. A follow-up telephone call will occur approximately 4 weeks after completion of the study.

Study Sponsor:

ALS Therapy Alliance (ATA) and Northeast ALS (NEALS) Consortium

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:

60

Estimated Study Start Date:

06/30/2013

Estimated Study Completion Date:

07/31/2014

Posting Last Modified Date:

06/30/2015

Date Study Added to alsconsortium.org:

05/22/2013
  • More Information
    July 1, 2015: ALS ACT will be funding further research
    http://www.alsa.o...ilot-studies.html
  • 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:

    N/A

    Can participants use Riluzole?

    Yes


    Study subjects meeting all of the following criteria will be allowed to enroll in the study:

    1. Sporadic ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
    2. Age 18 years or older.
    3. Disease duration ≤ 36 months from ALS symptom onset.
    4. Capable of providing informed consent and following trial procedures.
    5. Subjects must not have taken riluzole for at least 30 days or be on a 50 mg BID dose of riluzole for at least 60 days prior to randomization (riluzole-naïve subjects are permitted in the study).
    6. Subjects must not have taken medication for muscle cramping such as cyclobenzaprine, baclofen, carisoprodol, or methacarbamol, for at least 30 days prior to randomization or be on a stable dose for at least 60 days prior to randomization.
    7. Geographic accessibility to the site.
    8. 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.
    9. Slow vital capacity (SVC) measure ≥50% of predicted for gender, height, and age at the screening visit.
    10. Subjects medically able to undergo lumbar puncture (LP) as determined by the investigator (i.e., no bleeding disorder, allergy to local anesthetics, a skin infection at or near the LP site, or evidence of high intracranial pressure)
    11. Must be able to swallow capsules throughout the course of the study, according to PI judgment.
    12. Must have a caregiver assist with dispensing the study drug.

    Exclusion Criteria
    Study subjects meeting any of the following criteria during screening evaluations will be excluded from entry into the study:

    1. Invasive ventilator dependence, such as tracheostomy.
    2. Creatinine level greater than 1.5 mg/dL.
    3. SGOT (AST) / 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 60 days prior to Baseline Visit.
    10. Exposure to any other experimental agent (off-label use or investigational) within 30 days prior to Baseline Visit.
    11. Use of amiodarone, flecainide, duloxetine, tizanidine, or clozpine.
    12. Pregnant women or women currently breastfeeding.
    13. Placement of Diaphragm Pacing System (DPS) devise <60 days prior to Baseline Visit.
    14. Planned DPS device implantation after Baseline Visit.

  • Site Contact Information

    UCLA, Neuromuscular Research Center
    Rebecca Alvarez / .(JavaScript must be enabled to view this email address) / 310-825-5232
    Los Angeles, California 90095
    United States

    SUNY Upstate Medical Center
    Jennifer Moore / .(JavaScript must be enabled to view this email address) / 315-464-4619
    Syracuse, New York 13210
    United States

    University of Washington Medical Center
    Sharon Downing, RN / .(JavaScript must be enabled to view this email address) / 206-543-0081
    Seattle, Washington 98195
    United States