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Eur J Pain. 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.

Author information

1
Service de Pharmacologie Médicale, Direction de la Recherche Clinique et de l'Innovation, CETD, CIC, CNRS, SIGMA Clermont, ICCF, Service de Pharmacie, Université Clermont Auvergne, CHU Clermont-Ferrand, INSERM - NEURO-DOL, Clermont-Ferrand, France.
2
Analgesia Institute, Université Clermont Auvergne, Clermont-Ferrand, France.
3
CHU Amiens Picardie, CETD, CRC, Amiens, France.
4
Université Nice Côte-d'Azur, CHU Nice - Hôpital de Cimiez, Fédération Hospitalo-Universitaire INOVPAIN, CETD, Nice, France.
5
CHU Rouen, CETD, Rouen, France.
6
CH Lisieux, Lisieux, France.
7
CHU Saint-Etienne, CETD, Saint-Etienne, France.
8
Cancer Centre Oscar-Lambret, Lille, France.
9
CHU Grenoble Alpes, CETD, Grenoble, France.
10
CH Voiron, UETD, Voiron, France.
11
CH Lons-le-Saunier, CETD, Lons-le-Saunier, France.
12
Université Lille Nord de France, CHRU Lille, CETD, Lille, France.
13
CHU Nantes, CETD, Nantes, France.
14
AP-HP - Hôpital Raymond Poincaré, CETD, Paris, France.
15
CH Avranches, CETD, Avranches, France.
16
CHU Limoges, CETD, Limoges, France.
17
HCL - Hôpital Neurologique, CETD, Lyon, France.

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.

PMID:
29577519
DOI:
10.1002/ejp.1221
[Indexed for MEDLINE]

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