Evaluation of the Efficacy and Tolerance of Low Doses of Ethosuximide in the Treatment of Peripheral Neuropathic Pain

Study Overview
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Brief Summary
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Evaluation of the efficacy and tolerance of low doses of ethosuximide in the treatment of peripheral neuropathic pain

Detailed Description
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Multicenter, randomized, double-blind, placebo-controlled therapeutic trial evaluating the efficacy and safety of low doses of ethosuximide in neuropathic pain patients.

Official Title
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Evaluation of the Efficacy and Tolerance of Low Doses of Ethosuximide in the Treatment of Peripheral Neuropathic Pain

Conditions
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Peripheral Neuropathic Pain

Intervention / Treatment
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* Drug: Ethosuximide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female (under effective contraception: pill, implant, IUD, sterilization) aged 18 years or older, suffering from peripheral neuropathic pain (DN4 ≥ 4) for more than 3 months, of intensity ≥ 4 on a numerical scale from 0 to 10, and whose analgesic treatment has been stable for more than a month, Patients affiliated to the French Social Security system, Patients whose free and informed consent has been obtained. Exclusion Criteria: Pregnancy (βHCG+ blood) or breastfeeding, Neuropathic pain due to spinal cord or brain injury, phantom limb pain or algohallucinosis, Fibromyalgia or algodystrophy, Chronic pain syndrome that the patient cannot distinguish and/or is more intense than peripheral neuropathic pain, Significant abnormalities in liver (transaminases > 3N, cholestasis) and renal (MDRD < 60 mL/min) tests, Ongoing comorbidities: cancer, neurodegenerative pathology Severe depressive disorder in progress (as determined by the clinician), history of suicide attempts or hospitalization for depression, Diabetic patients (contraindicated due to the high sugar concentration of ethosuximide, 3g / 5 ml), Patients who have previously received ethosuximide (epilepsy or clinical trial), Surgery planned throughout the entire trial, Medical and surgical history incompatible with the study, Dependence on alcohol and/or drugs (for compliance purposes), Known allergy to succinimides (ethosuximide, methsuximide, phensuximide), Psychotic disorders, Epileptic patients, Patients benefiting from a legal protection measure (curatorship, guardianship, deprived of liberty or subject to judicial safeguard).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomisation 1:1 placebo or ethosuximide
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ethosuximide<br>Patients with chronic peripheral neuropathic pain | Drug: Ethosuximide<br>* Taking the treatment (1 daily intake during the evening meal) according to increasing dosage: Step 1: 2.5 ml (125 mg) / day for 7 days Step 2: 5 ml (250 mg) / day for 7 days Step 3: 7.5 ml (375 mg) / day for 7 days Step 4 (final): 10 ml (500 mg) / day for the remainder of the study (12 weeks).<br>|
| Placebo Comparator: Placebo<br>Patients with chronic peripheral neuropathic pain | Drug: Placebo<br>* Taking the treatment (1 daily intake during the evening meal) according to increasing dosage: Step 1: 2.5 ml (125 mg) / day for 7 days Step 2: 5 ml (250 mg) / day for 7 days Step 3: 7.5 ml (375 mg) / day for 7 days Step 4 (final): 10 ml (500 mg) / day for the remainder of the study (12 weeks).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathic pain intensity | Variation in pain intensity (NRS, Numerical Rating Scale 0-10) averaged over the 7 days prior to the start of treatment (D0) and over the last 7 days of treatment (12 weeks). | Day 0 | 
| Neuropathic pain intensity | Variation in pain intensity (NRS, Numerical Rating Scale 0-10) averaged over the 7 days prior to the start of treatment (D0) and over the last 7 days of treatment (12 weeks). | Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient's Global Impression of Change (PGIC scale) | Assessment of the patient's feelings about the effectiveness of the treatment. | Day 0, Day 28, Day 56, Day 84 | 
| Health related quality of life | Assessment of the patient's quality of life with EQ-5D-3L questionnaire | Day 0, Day 28, Day 56, Day 84 | 
| Quantitative sensory testing (QST) | Assessment of mechanical sensitivity using the von Frey test (static allodynia) and the brush test (dynamic allodynia). | Day 0, Day 28, Day 56, Day 84 | 
| adverse event | Assessment of the tolerability of the treatment by patients and clinicians | Throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ethosuximide, T-type calcium channel, Neuropathic pain