Effect of lacosamide in peripheral neuropathic pain: study protocol for a randomized, placebo-controlled, phenotype-stratified trial

• Published in: Current controlled trials in cardiovascular medicine Vol. 20; no. 1; p. 588
• Main Authors: Carmland, Malin E, Kreutzfeldt, Melissa, Holbech, Jakob V, Andersen, Niels T, Jensen, Troels S, Bach, Flemming W, Sindrup, Søren H, Finnerup, Nanna B
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.10.2019; BioMed Central; BMC
• Subjects: Analgesia; Analgesics; Analgesics - adverse effects; Analgesics - therapeutic use; Analysis; Biomarkers; Care and treatment; Clinical trials; Clinical Trials, Phase II as Topic; Denmark; Depression (Mood disorder); Double-Blind Method; Drug dosages; Duloxetine; Female; Genotype & phenotype; Humans; Lacosamide; Lacosamide - adverse effects; Lacosamide - therapeutic use; Male; Medical research; Multicenter Studies as Topic; Neuralgia - diagnosis; Neuralgia - drug therapy; Neurology; Neuropathic pain; Oxcarbazepine; Pain; Pain management; Pain Measurement; Patients; Phenotypes; Precision medicine; Quality of life; Randomized controlled trial; Randomized Controlled Trials as Topic; Sleep; Sleep disorders; Study Protocol; Time Factors; Treatment Outcome; Voltage-Gated Sodium Channel Blockers - adverse effects; Voltage-Gated Sodium Channel Blockers - therapeutic use; Denmark; Aarhus Denmark; Precision medicine; Randomized controlled trial; Lacosamide; Neuropathic pain
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-019-3695-7

Neuropathic pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite decades of research, it remains difficult to treat neuropathic pain. Lacosamide is a sodium-channel blocker that is efficacious in animal models of neuropathic pain. In humans, its effect in neuropathic pain is inconclusive, based on inconsistent results and very large placebo responses. Previous trials have not used patient stratification or looked for predictors for response. This study will be conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel, phase 2, proof-of-concept, phenotype-stratified study. The study will enroll 108 patients with peripheral neuropathic pain who will be randomized to a 12-week treatment with lacosamide or placebo up to 400 mg/day in a 2:1 ratio. The primary objective is to compare the change in the mean value of the patients' daily ratings of average pain intensity from baseline to the last week of treatment in patients with and without the irritable nociceptor phenotype in the per-protocol population. A supportive objective is to compare the effect of lacosamide with that of placebo in the two phenotypes. Secondary and tertiary outcomes include the Patient Global Impression of Change, pain relief, presence of 30% and 50% pain reduction, sleep disturbance, depression, and anxiety. We will examine the concept of individualized therapy based on phenotyping, and expect that this study will provide important information on the usefulness of lacosamide in the treatment of peripheral neuropathic pain. ClinicalTrials.gov, NCT03777956 . Registered on 18 December 2018.