Evidence map›Paper›PMID 26911633›Full record

Trial reportNeurology2016

A randomized trial of mexiletine in ALS: Safety and effects on muscle cramps and progression.

Michael D Weiss, Eric A Macklin, Zachary Simmons, Angela S Knox, David J Greenblatt, Nazem Atassi, Michael Graves, Nicholas Parziale, Johnny S Salameh, Colin Quinn and 9 more

Open access · greenAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 5 pooled it
7.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 5 syntheses or guidelines pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Efficacy of pain management strategies in adults with Amyotrophic Lateral Sclerosis (ALS): A Systematic Review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Pooled it
  3. Guideline
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Review
  9. Metabolomic analyses of amyotrophic lateral sclerosis, muscle cramps, and TJ-68 treatment.Metabolomics : Official journal of the Metabolomic Society · 2026
    Article
  10. Article
  11. Review
  12. Review
  13. Abnormalities of cortical stimulation strength-duration time constant in amyotrophic lateral sclerosis.Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2024
    Article
  14. Article
  15. Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.Annals of clinical and translational neurology · 2023
    Review
  16. Article
  17. Article
  18. Dependence of cortical neuronal strength-duration properties on TMS pulse shape.Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2023
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 1 institution in 1 country.

Michael D WeissFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City. mdweiss@uw.edu.
Eric A MacklinFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Zachary SimmonsFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Angela S KnoxFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
David J GreenblattFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Nazem AtassiFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Michael GravesFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Nicholas ParzialeFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Johnny S SalamehFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Colin QuinnFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Robert H BrownFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Jane B DistadFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Jaya TrivediFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Jeremy M ShefnerFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Richard J BarohnFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Alan PestronkFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Andrea SwensonFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Merit E CudkowiczFrom the Department of Neurology (M.D.W., J.B.D.), University of Washington Medical Center, Seattle; Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Z.S.), Penn State Hershey Medical Center, Hershey, PA; Department of Neurology (A.S.K., N.A., M.E.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Program in Pharmacology and Experimental Therapeutics (D.J.G.), Tufts University School of Medicine, Boston, MA; Department of Neurology (M.G., N.P.), UCLA Medical Center, Los Angeles, CA; Department of Neurology (J.S.S., C.Q., R.H.B.), University of Massachusetts Memorial Medical Center, Worcester; Department of Neurology (J.T.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (J.M.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (R.J.B.), University of Kansas Medical Center, Kansas City; Department of Neurology (A.P.), Washington University Medical Center, St. Louis, MO; and Department of Neurology (A.S.), University of Iowa Hospitals and Clinics, Iowa City.
Mexiletine ALS Study Group
Penn State Milton S. Hershey Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo determine the safety and tolerability of mexiletine in a phase II double-blind randomized controlled trial of sporadic amyotrophic lateral sclerosis (SALS).

methodsSixty participants with SALS from 10 centers were randomized 1:1:1 to placebo, mexiletine 300 mg/d, or mexiletine 900 mg/d and followed for 12 weeks. The primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetic study from plasma and CSF, ALS Functional Rating Scale-Revised (ALSFRS-R) score, slow vital capacity (SVC), and muscle cramp frequency and severity.

resultsThe only serious adverse event among active arm participants was one episode of imbalance. Thirty-two percent of participants receiving 900 mg of mexiletine discontinued study drug vs 5% on placebo (p = 0.026). Pharmacokinetic study demonstrated a peak plasma concentration 2 hours postdose and strong correlation between plasma and CSF (p < 0.001). Rates of decline of ALSFRS-R and SVC did not differ from placebo. Analysis of all randomized patients demonstrated significant reductions of muscle cramp frequency (300 mg: rate = 31% of placebo, p = 0.047; 900 mg: 16% of placebo, p = 0.002) and cramp intensity (300 mg: mean = 45% of placebo, p = 0.08; 900 mg: 25% of placebo, p = 0.005).

conclusionsMexiletine was safe at both doses and well-tolerated at 300 mg/d but adverse effects at 900 mg/d led to a high rate of discontinuation. Mexiletine treatment resulted in large dose-dependent reductions in muscle cramp frequency and severity. No effect on rate of progression was detected, but clinically important differences could not be excluded in this small and short-duration study. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that mexiletine is safe when given daily to patients with amyotrophic lateral sclerosis at 300 and 900 mg and well-tolerated at the lower dose.

Indexed as

Amyotrophic Lateral SclerosisDisease ProgressionDose-Response Relationship, DrugFemaleFollow-Up StudiesHumansMaleMexiletineMiddle AgedMuscle CrampPostural BalanceTreatment OutcomeVoltage-Gated Sodium Channel BlockersMexiletineVoltage-Gated Sodium Channel Blockers

Identifiers

PMID26911633
PMCPMC4836879
OpenAlexW2336547243

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.