Mexiletine for the treatment of muscle cramps in ALS

Study Purpose:

The purpose of this study is to evaluate the effectiveness of mexiletine for treating muscle cramps in ALS.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Not enrolling

Phase:

Phase IV

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

Bjorn Oskarsson, MD (UC Davis)
Craig McDonald, MD (UC Davis)

Clinicaltrials.gov ID (11 digit #):

NCT01811355

Neals Affiliated?

No

Coordinating Center Contact Information

University of California, Davis
Michelle Cregan / .(JavaScript must be enabled to view this email address) / (916) 734-6304
.(JavaScript must be enabled to view this email address) 4860 Y st, suite 1800
Sacramento, California 95817 United States

Full Study Summary:

Many ALS patients suffer from painful muscle cramps, but unfortunately we do not have any medication proven to help muscle cramps in ALS. Reducing the pain caused by cramps - which can be debilitating - could help people living with ALS.
Muscle cramps are sudden, painful, and involuntary contractions of a muscle. They are caused by nerve dysfunction. When we examine nerves and muscles electrically, we see cramps as bursts of high-frequency (up to150 Hz) firing of the motor nerve cells. Cramps in ALS are believed to be the result of an increase of persistent sodium currents in the sick lower motor nerve cells.
A medication called Quinine was for many years the commonly used drug for controlling cramps in ALS, but the FDA has advised against its use for cramps because of its potential risks (e.g., death). Today there is no agreement on how to treat cramps in the ALS. The American Academy of Neurology recently encouraged further studies of the treatment of muscle cramps and suggested lidocaine as one of a few drugs of special interest.

Mexiletine:
Mexiletine is a medication closely related to lidocaine that can be taken by mouth (instead of being injected). Mexiletine stops the type of sodium currents that are thought to cause muscle cramps. Mexiletine is a relatively older medication that has been extensively studied in humans. It has been shown to reduce the electrical measures of muscle cramps for other disease conditions. For example, in patients with another severe nerve disease - Machado-Joseph disease (SCA3) - mexiletine treatment led to a decrease in the average number of muscle cramps from 24 to 3 cramps per month.. The safety profile of mexiletine is good, with the most frequent side effects being nausea or other abdominal symptoms. These side effects are rare at the doses (300 mg/day) used in this study. In patients with normal heart function, mexiletine has a minimal effect on heart rhythm. In previous clinical trials, no subject developed any serious heart rate problem.

Experimental Plan:
Using multiple sites within the State of California we will quickly enroll a small number (N=30) of ALS patients with severe muscle cramps. The study is a double-blinded, placebo controlled (i.e., the investigator and the participant does not know if the pills contain mexiletine or placebo), crossover (all subjects receive two weeks of mexiletine and two weeks of placebo) study.
After a one week run in, participants will be evaluated on their ability to fill out the cramp diary. Participants who filled out their diary will be randomly assigned to either mexiletine or placebo for their first two weeks. For the first three days of each 2-week period, one 150mg capsule will be taken at bed time. For day 4 to 14 one capsule twice per day will be taken. Each treatment period will be 2 weeks with an intervening 1 week washout period - for a total study length of 6 weeks. Safety will be monitored with liver function studies and EKG's.

Study Sponsor:

UC Davis Neurology department

Participant Duration:

4 one hour visits over 6 weeks

Estimated Enrollment:

30

Estimated Study Start Date:

04/30/2013

Estimated Study Completion Date:

02/29/2016

Posting Last Modified Date:

04/30/2016

Date Study Added to alsconsortium.org:

05/31/2013
  • More Information
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    21

    Maximum Age:

    89

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    Inclusion Criteria:
    1. ALS diagnosed according to El Escorial criteria (Awaji version) as: Possible, Probable, or Definite.
    2. Experiencing cramps as a moderate or severe symptom as defined by willingness to take a medication for the symptom
    3. ≥2 cramps per day on average during run in week
    4. Life expectancy > 6 months, estimated by clinician
    5. Able to take drug capsule by mouth
    6. No significant EKG abnormality on screening
    7. aspartate aminotransferase / alanine aminotransferase / alkaline phosphatase <2x upper limit of normal measured at screening
    8. Having successfully filled out the cramp diary and cramp and fasciculation scales on six out of the last seven days of run in period

    Exclusion Criteria:
    1. Inability to communicate by telephone or email
    2. Allergy/ known sensitivity to mexiletine
    3. Prior use of mexiletine
    4. AV block unless subject has pacemaker
    5. Cardiac arrhythmia
    6. Prior myocardial infarction
    7. Other significant EKG abnormality
    8. Liver disease
    9. History of leucopenia (WBC <3,500/mm3)
    10. Epilepsy
    11. Other serious and unstable medical condition
    12. Pregnant woman
    13. Breastfeeding woman
    14. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
    15. Use of quinidine (alone or as a component of Nuedexta®) during the study
    16. Inability or unwillingness of subject to give written informed consent
    17. Woman of childbearing potential, not willing to use at least two approved methods of contraception
    18. Use of a prohibited medication during study
    19. Residing within the state of California (for subjects participating by Telemedicine).

  • Site Contact Information

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

    UCSD Department of Neurosciences ALS Clinical Trials (ACT) Program
    Ivy Chippendale or Aaryn Belfer / .(JavaScript must be enabled to view this email address) / 858-246-0247
    La Jolla, California 92093
    United States

    University of California, Davis
    Michelle Cregan / .(JavaScript must be enabled to view this email address) / (916) 734-6304
    4860 Y st, suite 1800
    Sacramento, California 95817
    United States

    UC Irvine Health ALS & Neuromuscular Center
    Brian Minton or Veronica Martin / .(JavaScript must be enabled to view this email address) / 714-456-8520 or 714-456-2332
    Orange, California 92868
    United States

    UCD Telehealth Network
    Bjorn Oskarsson, MD or Michelle Cregan Oskarsson, MD / .(JavaScript must be enabled to view this email address) / 916-734-6304
    One hundred sites, California Various
    United States