Subcutaneous Botulinum Toxin for Cutaneous Allodynia - Enriched Responder Trial

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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Subcutaneous Botulinum Toxin for Cutaneous Allodynia - Enriched Responder Trial

Conditions
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Pain

Intervention / Treatment
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* Drug: Botulinum Toxin Type A
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo then Botox<br>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<br>* Patients receive a subcutaneous injection of Botulinum Toxin Type A into the scar tissue<br>Drug: Saline<br>* Subcutaneous injection of saline into scar tissue<br>|
| Experimental: Botox then Placebo<br>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<br>* Patients receive a subcutaneous injection of Botulinum Toxin Type A into the scar tissue<br>Drug: Saline<br>* Subcutaneous injection of saline into scar tissue<br>|

What is the study measuring?
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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 |