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.
Eur J Pain
; 22(7): 1321-1330, 2018 08.
Article
in En
| MEDLINE
| ID: mdl-29577519
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 (11) 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.
Full text:
1
Collection:
01-internacional
Health context:
1_ASSA2030
Database:
MEDLINE
Main subject:
Calcium Channel Blockers
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Ethosuximide
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Chronic Pain
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Neuralgia
Type of study:
Clinical_trials
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Guideline
Limits:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Eur J Pain
Year:
2018
Document type:
Article