Botulinum Toxin Type A for Treating Allodynic Pain in SCI and MS

The Efficacy of Botulinum Toxin Type A in the Treatment of Allodynic-Type Neuropathic Pain in People With Spinal Cord Injury or Multiple Sclerosis

This study will examine the efficacy of Botulinum Toxin Type A ("Botox") in treating Allodynic-type neuropathic pain in people with spinal cord injury or multiple sclerosis.

Neuropathic pain is pain initiated or caused by injury to or disease of the nervous system, and is common in spinal cord injury patients or people with multiple sclerosis.

Allodynia is a type of neuropathic pain caused by something that normally would not cause pain, such as light touch, pressure from clothing, or bed sheets brushing against the skin.

Botox has been used to treat the muscle overactivity that causes spasticity in spinal cord injured patients. It has been noticed to exert some analgesic(pain relieving) effect, and has recently been studied as a treatment for neuropathic pain.

We want to see if Botox, injected intradermally, will relieve the symptoms of allodynic-type neuropathic pain.

24 volunteers are to be enrolled, with 16 receiving active treatment, and 8 "controls" receiving placebo.

Study Overview

• Status: Terminated
• Conditions: Neuropathic Pain; Allodynia
• Intervention / Treatment: Drug: Botulinum Toxin Type A; Drug: Normal Saline for Injection

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A IM4
      • WRHA Health Sciences Centre Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Fulfills the criteria for neuropathic pain causing allodynia according to IASP pain terminology.
• Allodynia that is resistant to, or has failed, the standard level of care measures for more that six months.
• Allodynia pain on a daily basis.
• Allodynia pain that scores at least 4/10 on a pain numerical scale.
• Other pain medications(including antidepressants and anticonvulsants)have been maintained at a stable dose for at least 2 months prior to enrollment.
• Ability to communicate in English.

Exclusion Criteria:

• Presence of other pain syndromes (e.g.,fibromyalgia, ongoing peripheral neuropathic pain.
• Allergy to Botulinum Toxin Type A.
• Allergy to albumin.
• Use of Botulinum Toxin Type A for other treatment indications in the 3 months prior to enrollment.
• Renal failure.
• Hepatic failure.
• Neuromuscular junction disorders.
• Bleeding diathesis.
• Cognitive impairment, dementia, major depression or psychotic disorder.
• Pregnant or breastfeeding.
• Infection at the injection site.
• Active alchohol or substance abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Botulinum Toxin Type A; 200 units of Botulinum Toxin Type a will be administered intradermally to the allodynic area chosen for study.The allodynic area will be mapped, and the number of injections needed to cover the allodynic area without exceeding 40 injection sites will be determined. All participants will receive a cream formulation of lidocaine and prilocaine (EMLA) applied to the painful area 60 minutes before the injections to minimize any discomfort caused by the injections.	Drug: Botulinum Toxin Type A
Placebo Comparator: Arm 2: Normal Saline for Injection; Normal saline for intradermal injection will be prepared by the Investigational Pharmacy in a manner as to be indistinguishable from active drug. The allodynic area will be mapped so as to determine the number of injections needed to cover the whole allodynic area without exceeding 40 injection sites. All participants will receive a cream formulation of lidocaine and prilocaine (EMLA) applied to the painful area 60 minutes before the injections to minimize any pain caused by the injections.	Drug: Normal Saline for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brief Pain Inventory	The primary outcome measure will be the self-reported average pain intensity from each morning's record in a diary. The average(self-reported) pain intensity will be measured at the screening visit, then the daily diary will be dispensed. The diary will ask for the average pain intensity of the last 24 hours using an 11-point numerical scale, with 0 representing no pain and 10 representing the worst pain imaginable	Baseline and daily until study completion at 13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropathic Pain Symptom Inventory	This scale rates the mean intensity of 10 neuropathic pain symptoms and their combination into 5 distinct dimensions during the last 24 hours on an 11-point (0-10) numerical scale	Baseline and follow-up visits(at weeks 1, 4, 8 and 13)
The Hospital Anxiety and Depression Scale	14 items scored as anxiety and depression	Baseline and follow-up visits (at weeks 1, 4, 8 and 13).
Daily Sleep Interference Scale	Asks if pain interfered with sleep in the past 24 hours,using an 11-point scale (O-pain did not interfere with sleep, 10-pain completely interfered with sleep). Dispensed at baseline.	Baseline and daily during study period until week 13.
Clinician Global Impression Scale	Assesses the clinician's impression of Efficacy and Tolerability of study medication using a 4-point scale, with 1 being Very good, and 4 being Poor	Final visit at week 13
Patient's Global Impression Scale	Measures the patients global impression of the efficacy and tolerability of the study medication on a 4-point scale, with 1 representing very good, and 4 representing poor	Final visit at week 13

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of brush-induced allodynia	The area of skin with allodynic pain is stroked with a standardized brush and the patient reports any pain associated with the stroking.	Baseline and follow-up visits(weeks 1, 4, 8 and 13)
Measurement of mechanical sensations and pain thresholds	An algometer (a device that pushes against the skin to measure when pain is felt) will be used on the allodynic area	Baseline and follow-up visits (weeks 1, 4 , 8 and 13)
Recording Area of allodynia	The area of allodynic pain to be treated is traced on transparent paper	Baseline and follow-up visits (at weeks 1, 4, 8 and 13)
Measurement of temperature sensations and pain thresholds	A thermo-test is used to measure temperature sensations and pain thresholds in the allodynic area	Baseline and follow-up visits(at weeks 1, 4, 8 and 13)

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Allergan
• Investigators: Principal Investigator: Karen Ethans, MD, Health Sciences Centre

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: July 25, 2013
• First Submitted That Met QC Criteria: July 26, 2013
• First Posted (Estimate): July 30, 2013

Study Record Updates

• Last Update Posted (Estimate): October 2, 2015
• Last Update Submitted That Met QC Criteria: October 1, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Sensation Disorders; Somatosensory Disorders; Neuralgia; Hyperalgesia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: Botox 2013