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

Study Purpose:

The purpose of this 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.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Active, currently recruiting

Phase:

Phase II

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

Michael Weiss, MD, Washington University

Clinicaltrials.gov ID (11 digit #):

NCT02781454

Neals Affiliated?

Yes

Coordinating Center Contact Information

MGH - NCRI
David Klements, MS / .(JavaScript must be enabled to view this email address) / 617-726-3430
Emily Engel / .(JavaScript must be enabled to view this email address) / 617-724-7210
165 Cambridge Street
6th Floor
Boston, Massachusetts 02114 United States

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).

Study Sponsor:

ALSA; ALSFAC

Participant Duration:

8 Weeks

Estimated Enrollment:

60

Estimated Study Start Date:

10/01/2016

Estimated Study Completion Date:

05/30/2018

Posting Last Modified Date:

08/10/2017

Date Study Added to alsconsortium.org:

06/27/2016
  • 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

    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

    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

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

    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

    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

    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