Introduction: Currently available analgesics are ineffective in 30-50% of patients suffering from neuropathic pain and often induce deleterious side effects. T-type calcium channel blockers (mibefradil, ethosuximide, NNC 55-0396) are of great interest for the development of new symptomatic treatments of neuropathic pain, due to their various effects on pain perception. Interestingly, ethosuximide, which has already been approved for treating epilepsy, is available on the European market for clinical use. Despite numerous preclinical data demonstrating an antinociceptive effect of ethosuximide in various animal models of neuropathic pain, no clinical studies have been published to date on the analgesic efficacy of ethosuximide in patients with neuropathic pain. Methods and analysis: The Ethosuximide in the Treatment of non-Diabetic Peripheral Neuropathic Pain (EDONOT) trial is a randomised, parallel, controlled, double-blinded, multicentre clinical study. It is the first clinical trial to evaluate the efficacy and safety of ethosuximide in the treatment of non-diabetic peripheral neuropathic pain. Adult patients exhibiting peripheral neuropathic pain (Numeric Rating Scale (NRS) ≥4 and Douleur Neuropathique 4 (DN4)≥4) for at least 3 months and under stable analgesic treatment for at least 1 month will be included. Patients (n=220) will be randomly assigned to receive either ethosuximide or control treatment for 6 weeks following a 1 week run-in period. The primary end point is the intensity of neuropathic pain, assessed by NRS (0-10) before and after 6 weeks of treatment. The secondary end points are safety (adverse events are collected during the study: daily by the patient on the logbook and during planned phone calls by investigators), the intensity and features of neuropathic pain (assessed by Brief Pain Inventory (BPI) and Neuropathic Pain Symptom Inventory (NPSI) questionnaires) and health-related quality of life (assessed by Medical Outcome Study Short Form 12 (MOS SF-12) and Leeds questionnaires). Ethics and communication: The study was approved by an independent ethics committee (CPP Sud-Est VI, France, IRB00008526) and registered by the French competent authority (Agence nationale de sécurité du médicament (ANSM)). Trial registration number: NCT02100046, Recruiting.