Subcutaneous Botulinum Toxin for Cutaneous Allodynia - Enriched Responder Trial

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: Terminated
• Conditions: Pain
• Intervention / Treatment: Drug: Botulinum Toxin Type A; Drug: Saline

Detailed Description

Patients with post-herpetic neuralgia, complex regional pain syndrome, and 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): 5
• 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 to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Moderate to severe pain (greater than 2/10) of duration more than 6 months despite previous therapy, excluding botox injection
• The patient exhibits at least 80% pain relief following injection of local anesthetic subcutaneously into scar as assessed by change in NRS
• Patient reports more than 3 weeks of greater than 50% pain relief from previous botox injection
• The patient reports the presence of hyperalgesia, allodynia, dysesthesia, or hypoesthesia surrounding the scar in the absence of the botox injection
• Age 18-100
• Ability to read, write, and converse in English, provide informed consent, and follow study procedures

Exclusion Criteria:

• Any neuromuscular disorder such as myasthenia gravis, eaton lambert, muscular dystrophy
• Any ongoing legal action related to their pain
• Allergy to local anesthetics
• Any ongoing disability claim
• Currently being treated for any severe psychiatric disorder, including anxiety or depression
• History of any adverse reaction to botulinum toxin
• History of botulism
• Untreated infection
• Coagulopathy
• (Females) - positive pregnancy test
• Surgery in the last 6 months

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; Injection 1: Saline- Subcutaneous injection of saline into scar tissue Injection 2: Botulinum Toxin Type A- Patients receive a subcutaneous injection of Botulinum Toxin Type A into the scar tissue	Drug: Botulinum Toxin Type A; Patients receive a subcutaneous injection of Botulinum Toxin Type A into the scar tissue; Drug: Saline; Subcutaneous injection of saline into scar tissue
Experimental: Botox then Placebo; Injection 1: Botulinum Toxin Type A- Patients receive a subcutaneous injection of Botulinum Toxin Type A into the scar tissue Injection 2: Saline- Subcutaneous injection of saline into scar tissue	Drug: Botulinum Toxin Type A; Patients receive a subcutaneous injection of Botulinum Toxin Type A into the scar tissue; Drug: Saline; Subcutaneous injection of saline into scar tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Analgesic Failure	Participants completed the Pain Numeric Rating Scale everyday after the injections. Outcome measure represents the number of days before pain returned to baseline levels.	Duration of trial (2-20 months, depending on how long pain relief lasts)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Psychosocial Function as Assessed by Outcomes as Dictated by the IMMPACT Guidelines	The Beck Depression Inventory was used to assess psychosocial function. Scores were measured at baseline, their final questionnaire following the first injection visit, and their final questionnaire following their second injection visit. Scores range from 0-63, with lower scores representing less severe depression symptoms and higher scores representing more severe depression symptoms.	Duration of trial (2-20 months, depending on how long pain relief lasts)
NRS Score Three Weeks After Injection	Pain scores were measured at baseline, 3 weeks after placebo, and 3 weeks after botox. Scores range from 0 (no pain) to 10 (severe, disabling pain).	3 weeks after injection

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: January 14, 2009
• First Submitted That Met QC Criteria: January 14, 2009
• First Posted (Estimate): January 15, 2009

Study Record Updates

• Last Update Posted (Actual): August 15, 2017
• Last Update Submitted That Met QC Criteria: July 14, 2017
• Last Verified: July 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-01072009-1499; 15601