Mexiletine for the Treatment of Muscle Cramps in ALS

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of California, Davis
Sponsor:
Collaborators:
University of California, Davis
ALS Association
Information provided by (Responsible Party):
Bjorn Oskarsson, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT01811355
First received: March 6, 2013
Last updated: June 22, 2014
Last verified: June 2014

March 6, 2013
June 22, 2014
May 2013
June 2015   (final data collection date for primary outcome measure)
Cramp diary [ Time Frame: Daily during the 6 week study ] [ Designated as safety issue: No ]
Daily recording of number of muscle cramps that occurred in the last 24 hours.
Same as current
Complete list of historical versions of study NCT01811355 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Mexiletine for the Treatment of Muscle Cramps in ALS
Mexiletine for the Treatment of Muscle Cramps in ALS

The purpose of this study is to determine if mexiletine is effective for the treatment of muscle cramps in Amyotrophic Lateral Sclerosis (ALS).

Background:

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Muscle Cramps in Amyotrophic Lateral Sclerosis
  • Drug: Mexiletine
    Other Name: Mexetil
  • Drug: Placebo
    Other Name: Sugar pill
  • Active Comparator: Mexiletine
    Mexiletine, capsule, 150mg, PO BID, 14 days
    Intervention: Drug: Mexiletine
  • Placebo Comparator: Placebo
    Placebo, capsule, PO BID, 14 days
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
July 2015
June 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • ALS diagnosed according to El Escorial criteria (Awaji version) as: Possible, Probable, or Definite.
  • Experiencing cramps as a moderate or severe symptom as defined by willingness to take a medication for the symptom
  • ≥4 cramps per day on average during run in week
  • Life expectancy > 6 months, estimated by clinician
  • Able to take drug capsule by mouth
  • No significant EKG abnormality on screening
  • aspartate aminotransferase / alanine aminotransferase / alkaline phosphatase <2x upper limit of normal measured at screening
  • 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:

  • Inability to communicate by telephone or email
  • Allergy/ known sensitivity to mexiletine
  • Prior use of mexiletine
  • AV block unless subject has pacemaker
  • Cardiac arrhythmia
  • Prior myocardial infarction
  • Other significant EKG abnormality
  • Liver disease
  • History of leucopenia (WBC <3,500/mm3)
  • Epilepsy
  • Other serious and unstable medical condition
  • Pregnant woman
  • Breastfeeding woman
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Use of quinidine (alone or as a component of Nuedexta®) during the study
  • Inability or unwillingness of subject to give written informed consent
  • Woman of childbearing potential, not willing to use at least two approved methods of contraception
  • Use of a prohibited medication during study
Both
21 Years to 89 Years
No
Contact: Bjorn Oskarsson, MD 916 734 4660 bjorn.oskarsson@ucdmc.ucdavis.edu
Contact: Michelle Cregan (916) 734-6304 michelle.cregan@ucdmc.ucdavis.edu
United States
 
NCT01811355
378164-3
No
Bjorn Oskarsson, MD, University of California, Davis
Bjorn Oskarsson, MD
  • University of California, Davis
  • ALS Association
Principal Investigator: Bjorn Oskarsson, MD UC Davis
University of California, Davis
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP