Botulinum Toxin in Peripheral Neuropathic Pain

• ClinicalTrials.gov Identifier: NCT01251211
• Recruitment Status: Completed
• First Posted: December 1, 2010
• Last Update Posted: March 11, 2016
• Sponsor: Hospital Ambroise Paré Paris
• Information provided by (Responsible Party): Nadine ATTAL, Hospital Ambroise Paré Paris

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Postherpetic Neuralgia; Diabetic Polyneuropathies; Other Polyneuropathies	Drug: botulinum toxin type A	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2010
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: botulinum toxin type A; botulinum toxin type A will be injected subcutaneously in the painful area (maximum 300 units)	Drug: botulinum toxin type A; 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; Other Name: botox
Placebo Comparator: sodium chloride 9 %; sodium chloride 9 % will be used as a neutral placebo	Drug: botulinum toxin type A; 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; Other Name: botox

Outcome Measures

Primary Outcome Measures :

1. Average pain intensity on numerical scales in a self diary by the patient [ Time Frame: every day from baseline for up to 6 months ]
   Numerical scales (0-10)

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Evaluate the therapeutic gain of the second injection [ Time Frame: Throughout the study up to 6 months ]
   Evaluate whether the second injection is associated with significant therapeutic gain on average pain intensity over 6 months
2. Evaluate pain relief at 24 weeks [ Time Frame: 24 weeks ]
   pain relief scale

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Brazil

Divisão de Clínica Neurológica do Hospital das Clínicas da FMUSP

Sao Paulo, Brazil

France

Hôpital Ambroise Paré, APHP

Boulogne-Billancourt, France, 92100

Hôpital Dupuytren

Limoges, France

Sponsors and Collaborators

Hospital Ambroise Paré Paris

Investigators

• Study Director: Nadine ATTAL, MD PhD; APHP and INSERM

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Attal N, de Andrade DC, Adam F, Ranoux D, Teixeira MJ, Galhardoni R, Raicher I, Uceyler N, Sommer C, Bouhassira D. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2016 May;15(6):555-65. doi: 10.1016/S1474-4422(16)00017-X. Epub 2016 Mar 2.

• Responsible Party: Nadine ATTAL, Clinical principal investigator, Hospital Ambroise Paré Paris
• ClinicalTrials.gov Identifier: NCT01251211
• Other Study ID Numbers: BOTNEP
• First Posted: December 1, 2010
• Last Update Posted: March 11, 2016
• Last Verified: March 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Nadine ATTAL, Hospital Ambroise Paré Paris:

BOTULINUM TOXIN; NEUROPATHIC PAIN; RANDOMIZED CONTROLLED TRIAL

Additional relevant MeSH terms:

Neuralgia; Polyneuropathies; Neuralgia, Postherpetic; Diabetic Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents