- A trial of mexiletine, a drug that is FDA-approved to treat cardiac rhythm abnormalities and in use to treat muscle cramps and pain, was conducted in 60 ALS patients by the Northeast Amyotrophic Lateral Sclerosis (NEALS) Consortium; a webinar summarizing the results is now available on the NEALS website.
- The rationale for conducting the trial was that the drug might be helpful for treating ALS-associated muscle cramping and that experiments in mice had shown it could also have protective effects on nerve cells.
- The results of the three-arm study (two groups on different doses of mexiletine and one placebo group) found that the drug was reasonably safe and well tolerated and that it reduced the frequency and intensity of muscle cramps; it did not, however, affect motor or respiratory function.
Preliminary results of a trial of mexiletine in 60 people with amyotrophic lateral sclerosis (ALS) show the drug is reasonably safe and well tolerated and possibly effective for reducing the frequency and intensity of muscle cramps associated with this disorder. However, no benefits were seen in mexiletine recipients versus placebo recipients on tests of motor or respiratory function.
A webinar for the ALS community was presented on Nov. 21, 2014, and is now archived on the website of the Northeast ALS (NEALS) Consortium. You can watch and listen to a replay of the webinar by registering at Mexiletine Webinar.
Michael Weiss, a professor of neurology at the University of Washington School of Medicine in Seattle and the principal investigator for this phase 2 study of mexiletine in ALS, presented the preliminary findings.
Mexiletine prolonged survival in mice with ALS-like disease
Weiss explained that mexiletine is approved by the U.S. Food and Drug Administration (FDA) for the treatment of cardiac rhythm abnormalities and that it is also used to treat certain types of pain arising from disorders of the nervous system and to treat myotonia (difficulty relaxing muscles, experienced as muscle cramps).
The rationale for trying mexiletine in ALS, Weiss explained, was that many people with this disease experience troublesome muscle cramps; and that, in mice with an ALS-like disease, mexiletine actually prolonged survival, suggesting it might have a protective effect on nerve cells.
About the phase 2 trial
The phase 2 trial, conducted at multiple centers, was primarily to determine the safety and tolerability of mexiletine in ALS patients, with secondary goals of determining the levels of mexiletine in blood and spinal fluid and any possible effects on motor function, muscle cramp frequency or intensity, or a respiratory measurement called slow vital capacity (SVC).
The 60 trial participants were randomly assigned to receive 300 milligrams of mexiletine per day, 900 milligrams of mexiletine per day, or a placebo for 12 weeks.
Mexiletine appeared safe, with benefit for cramping
The investigators did not see adverse effects on heart rhythm, which had been a concern. However, tremors and nausea occurred in patients on the higher dosage significantly more often than in the placebo group or the group taking the lower dosage.
They did not see any change in the ALS Functional Rating Scale, which measures motor function, in either mexiletine group compared to the placebo group. A slowing of the decline in respiratory function was seen in the lower-dose mexiletine group, but it was not statistically significant.
Mexiletine levels in blood and spinal fluid were not available as of the Nov. 21 presentation.
When mexiletine was compared to a placebo, the researchers did see a reduction in the frequency of muscle cramps – more so in the higher-dose than the lower-dose group – and in the intensity of muscle cramps in the higher-dose group. These findings led Weiss to comment, "It might be reasonable to consider using mexiletine for muscle cramps in patients with ALS."