Subcutaneous Botulinum Toxin for Cutaneous Allodynia

Superficial injection of Botulinum toxin has been advocated for cosmetic purposes but has also been reported to be helpful for some pain conditions. The investigators have observed prolonged profound analgesia following subcutaneous superficial injection of Botulinum Toxin Type A (BTA) in patients with certain types of neuropathic pain. The investigators propose to study if addition of BTA extends pain relief compared to placebo when injected subcutaneously into areas of cutaneous allodynia (the property that a normally non-noxious stimulus is perceived as painful).

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Placebo - Saline; Drug: Botulinum Toxin A

Detailed Description

Post-surgical neuromatous pain patients have marked cutaneous allodynia. Touching their skin with normally non-painful stimuli results in pain. Injected local anesthetics are often effective in providing temporary relief. In the course of clinical practice the investigators have observed that a number of patients with cutaneous allodynia have had marked persistent benefit from subcutaneous injection of Botulinum toxin Type A.

Rather than killing targeted neurons, Botulinum toxin type A inhibits release of acetylcholine from cholinergic nerve terminals in a prolonged but ultimately reversible manner. Neuropathic pain and its hallmark allodynia are classically difficult to treat. Standard treatment with tricyclic antidepressants, anti-epileptic drugs, opiates and spinal cord stimulation is frequently disappointing leaving patients with refractory pain. Surgical or percutaneous ablation of involved nerves has fallen out of favor among many due to disappointing results.

A pilot study is needed to assess the efficacy of superficially injected Botulinum Toxin type A for treatment of cutaneous allodynia and spontaneous pain among patients with neuropathic pain.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:- Moderate to severe pain (greater than 4/10) of duration more than 6 months despite previous therapy.

• The patient exhibits at least 80% pain relief following injection of local anesthetic subcutaneously into scar as assessed by change in NRS
• The patient reports the presence of hyperalgesia, allodynia, dysesthesia, or hypoesthesia surrounding the scar
• Age 18-100
• Ability to read, write, and converse in English, provide informed consent, and follow study procedures

Exclusion Criteria:

1. Any neuromuscular disorder such as myasthenia gravis, eaton lambert, muscular dystrophy
2. Any ongoing legal action related to their pain
3. Allergy to local anesthetics
4. A current or history of any severe psychiatric disorder
5. History of any adverse reaction to botulinum toxin
6. History of botulism
7. Untreated infection
8. Coagulopathy
9. Females - positive pregnancy test
10. Surgery within the past 6 months at the site of the painful scar

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo then Botox	Drug: Placebo - Saline; Subcutaneous Saline injection given at site of scar neuroma
Experimental: Botox then Placebo	Drug: Botulinum Toxin A; Subcutaneous injection of Botulinum Toxin Type A into the patient's scar tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Until Analgesic Failure	Participants made daily NRS reports via Palm Pilot, and "failure" was defined as (Pre-injection baseline NRS) - (Mean NRS for any 3 preceding days) ≤ 0; or 9 months	Each participant was assessed for up to 224 days per intervention (injection) or until they returned to NRS baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NRS Score Three Weeks After Injection	The NRS scores range from 0-100, where 0 indicated no pain and 100 indicated the worst pain.	Three weeks after injection

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Sean Mackey, Stanford University

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: July 28, 2008
• First Submitted That Met QC Criteria: July 28, 2008
• First Posted (Estimate): July 30, 2008

Study Record Updates

• Last Update Posted (Actual): October 25, 2017
• Last Update Submitted That Met QC Criteria: October 23, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; 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: SU-01072008-965; 11830