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Randomized Controlled Trial
. 2018 Aug;22(7):1321-1330.
doi: 10.1002/ejp.1221. Epub 2018 Apr 18.

Efficacy and safety of a T-type calcium channel blocker in patients with neuropathic pain: A proof-of-concept, randomized, double-blind and controlled trial

N Kerckhove  1   2 , B Pereira  1 , S Soriot-Thomas  3 , H Alchaar  4 , R Deleens  5 , V S Hieng  6 , E Serra  3 , M Lanteri-Minet  1   4 , P Arcagni  7 , P Picard  1 , D Lefebvre-Kuntz  8 , C Maindet  9 , G Mick  10 , L Balp  11 , C Lucas  12 , C Creach  7 , M Letellier  13 , V Martinez  14 , M Navez  7 , D Delbrouck  8 , E Kuhn  13 , E Piquet  4 , E Bozzolo  4 , C Brosse  7 , B Lietar  7 , F Marcaillou  1 , A Hamdani  8 , N Leroux-Bromberg  8 , Y Perier  15 , P Vergne-Salle  16 , C Gov  17 , N Delage  1 , D Gillet  10 , S Romettino  4 , D Richard  1 , C Mallet  1 , L Bernard  1 , C Lambert  1 , C Dubray  1   2 , C Duale  1   2 , A Eschalier  1   2
Affiliations
Randomized Controlled Trial

Efficacy and safety of a T-type calcium channel blocker in patients with neuropathic pain: A proof-of-concept, randomized, double-blind and controlled trial

N Kerckhove et al. Eur J Pain. 2018 Aug.

Abstract

Background: T-type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T-type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain.

Methods: This proof-of-concept, multicentre, double-blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add-on therapy) to an inactive control (IC) in 114 patients with non-diabetic peripheral neuropathic pain. After a 7-day run-in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention-to-treat population. This study is registered with EudraCT (2013-004801-26) and ClinicalTrials.gov (NCT02100046).

Results: The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per-protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI -25.8; -5.4) from baseline compared to IC (-7.8%, 95% CI -14.3; -1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients.

Conclusion: Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events.

Significance: This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per-protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T-type calcium channel inhibition for the treatment of neuropathic pain.

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