Mexiletine for the Treatment of Muscle Cramps in ALS
|ClinicalTrials.gov Identifier: NCT01811355|
Recruitment Status : Completed
First Posted : March 14, 2013
Results First Posted : June 27, 2017
Last Update Posted : August 28, 2017
|Condition or disease||Intervention/treatment||Phase|
|Muscle Cramps in Amyotrophic Lateral Sclerosis||Drug: Mexiletine Drug: Placebo||Phase 4|
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 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.
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Mexiletine for the Treatment of Muscle Cramps in ALS|
|Study Start Date :||May 2013|
|Primary Completion Date :||March 2016|
|Study Completion Date :||May 2016|
U.S. FDA Resources
Active Comparator: Mexiletine
Mexiletine, capsule, 150mg, PO BID, 14 days
Sodium channel blocker
Other Name: Mexetil
Placebo Comparator: Placebo
Placebo, capsule, PO BID, 14 days
Other Name: Sugar pill
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01811355
|United States, California|
|UCD Telehealth Network - Lake Almanor Clinic|
|Chester, California, United States, 96020|
|UCSD Department of Neurosciences ALS Clinical Trials (ACT) Program|
|La Jolla, California, United States, 92093|
|UCLA Neuromuscular Research Program|
|Los Angeles, California, United States, 90095|
|UCD Telehealth Network|
|Multiple Locations, California, United States, Various|
|UC Irvine Health ALS & Neuromuscular Center|
|Orange, California, United States, 92868|
|UC, Davis Medical Center ALS Clinic|
|Sacramento, California, United States, 95817|
|Principal Investigator:||Bjorn Oskarsson, MD||UC Davis|