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Mexiletine for the Treatment of Muscle Cramps in ALS

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ClinicalTrials.gov Identifier: NCT01811355
Recruitment Status : Completed
First Posted : March 14, 2013
Results First Posted : June 27, 2017
Last Update Posted : August 28, 2017
Sponsor:
Collaborators:
University of California, Davis
ALS Association
Information provided by (Responsible Party):
Bjorn Oskarsson, MD, University of California, Davis

Tracking Information
First Submitted Date  ICMJE March 6, 2013
First Posted Date  ICMJE March 14, 2013
Results First Submitted Date  ICMJE April 3, 2017
Results First Posted Date  ICMJE June 27, 2017
Last Update Posted Date August 28, 2017
Study Start Date  ICMJE May 2013
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2017)
  • Daily Muscle Cramps [ Time Frame: 6 weeks ]
    The average of the daily recording of number of muscle cramps that occurred in the last 24 hours- over a 6 week period.
  • Cramp Severity [ Time Frame: 6 weeks ]
    Daily cramp severity was rated on the 100-unit visual analog scale. Scores ranged from 0 to 100, with 100 being the greatest amount of cramp severity
Original Primary Outcome Measures  ICMJE
 (submitted: March 12, 2013)
Cramp diary [ Time Frame: Daily during the 6 week study ]
Daily recording of number of muscle cramps that occurred in the last 24 hours.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mexiletine for the Treatment of Muscle Cramps in ALS
Official Title  ICMJE Mexiletine for the Treatment of Muscle Cramps in ALS
Brief Summary The purpose of this study is to determine if mexiletine is effective for the treatment of muscle cramps in Amyotrophic Lateral Sclerosis (ALS).
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Muscle Cramps in Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Drug: Mexiletine
    Sodium channel blocker
    Other Name: Mexetil
  • Drug: Placebo
    Placebo
    Other Name: Sugar pill
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 23, 2017)
23
Original Estimated Enrollment  ICMJE
 (submitted: March 12, 2013)
30
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • ≥2 cramps per week 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 <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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01811355
Other Study ID Numbers  ICMJE 378164
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bjorn Oskarsson, MD, University of California, Davis
Study Sponsor  ICMJE Bjorn Oskarsson, MD
Collaborators  ICMJE
  • University of California, Davis
  • ALS Association
Investigators  ICMJE
Principal Investigator: Bjorn Oskarsson, MD UC Davis
PRS Account University of California, Davis
Verification Date July 2017

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