Botulinum Toxin in Peripheral Neuropathic Pain

Study Overview
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Brief Summary
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Pain due to peripheral nerve lesion remains extremely difficult to treat and current treatments have onl moderate efficacy and/or side effects. The investigators have previously demonstrated the long term efficacy of Botulinum toxin type A (BTX-A) in a small group of patients with post-traumatic/postherpetic neuralgia and allodynia. The present study aims to a/ confirm the efficacy of repeated applications of BTX-A in a larger group of patients with peripheral neuropathic pain with or without allodynia(primary outcome) ; b/ evaluate its mechanisms of action ; c/analyse the predictors of response ;d/analyse whether the second injection is associated with a therapeutic gain. This will be a randomized placebo controlled study. A total of 30 patients will be randomized to receive either BTX-A (subcutaneous injection in the painful area) or placebo. Each injection will be repeated within at least 3 months depending on the duration of efficacy. Skin punch biopsies will be performed before and 1 month after BTX-A administration. The investigators postulate that this study will confirm the clinical efficacy and good safety of repeated administrations of BTX-A in the treatment of peripheral neuropathic pain.

Official Title
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Randomized Double Blind Placebo Controlled Multicenter Study of the Efficacy and Safety of Repeated Administrations of Botulinum Toxin Type A (Botox) in the Treatment of Peripheral Neuropathic Pain

Conditions
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Postherpetic Neuralgia, Diabetic Polyneuropathies, Other Polyneuropathies

Intervention / Treatment
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* Drug: botulinum toxin type A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 18 to 85 years Spontaneous pain with a minimal intensity of 4/10 on numerical scle Pain present for at least 6 months Pain related to painful mononeuropathy or sensory polyneuropathy Able to understand the protocol and comply to the requirements of the study Written informed consent Painful area limited to a maximum of 240 cm2 Exclusion Criteria: Facial pain Litigation (pending) Unstable condition responsible for neuropathic pain (ie, unstable immunological disease...) HIV or chemotherapy induced neuropathy Contraindications to BTX-A (neuromuscular disease, hypersensitivity, infection, coagulation disorder, pregnancy) Other pain more severe than neuropathic pain No compliance with the self diary Drug abuse or alcoholism Severe major depression Cognitive impairment Other research protocol within the last 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: botulinum toxin type A<br>botulinum toxin type A will be injected subcutaneously in the painful area (maximum 300 units) | Drug: botulinum toxin type A<br>* BTX A : 5 units/0.2 ml, maximum 300 units will be injected subcutaneous in the painful area ; this will be performed after randomization and within a minimum of 3 months interval depending on the duration of efficacy (maximum 6 months) Saline will be injected in the same volume in the painful area within the same frequency<br>* Other names: botox;|
| Placebo Comparator: sodium chloride 9 %<br>sodium chloride 9 % will be used as a neutral placebo | Drug: botulinum toxin type A<br>* BTX A : 5 units/0.2 ml, maximum 300 units will be injected subcutaneous in the painful area ; this will be performed after randomization and within a minimum of 3 months interval depending on the duration of efficacy (maximum 6 months) Saline will be injected in the same volume in the painful area within the same frequency<br>* Other names: botox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average pain intensity on numerical scales in a self diary by the patient | Numerical scales (0-10) | every day from baseline for up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of treatment on neuropathic symptoms | Neuropathic Pain Symptom Inventory will be used to assess symptoms | at each visit | 
| Quality of life VAS | This will be assessed using the EuroQol questionnaire | at each visit | 
| Intensity of allodynia to brush | This will performed using a brush | at each visit | 
| assessment of effects of BTX-A on substance P and CGRP | This will be performed using skin punch biopsies in the painful area | at baseline and 1 month after BTX-A or placebo | 
| Side effects | side effects of BTX-A will be assessed | throughout the study and each each visit | 
| Detection and pain thresholds to mechanical and thermal stimuli and responses to suprathreshold stimuli | this will use quantitative sensory testing (thermotest, Von Frey filaments) | at each visit | 
| Predictors of the response | We will assess the predictors of the response to BTX-A based on baseline pain thresholds, presence and severity of allodynia, skin punch biopsy and catastrophizing | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BOTULINUM TOXIN, NEUROPATHIC PAIN, RANDOMIZED CONTROLLED TRIAL