Pain
Conditions
Brief summary
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
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.
Interventions
DRUGBotulinum Toxin Type A
Patients receive a subcutaneous injection of Botulinum Toxin Type A into the scar tissue
DRUGSaline
Subcutaneous injection of saline into scar tissue
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Analgesic Failure | Duration of trial (2-20 months, depending on how long pain relief lasts) | Participants completed the Pain Numeric Rating Scale everyday after the injections. Outcome measure represents the number of days before pain returned to baseline levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Psychosocial Function as Assessed by Outcomes as Dictated by the IMMPACT Guidelines | Duration of trial (2-20 months, depending on how long pain relief lasts) | 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. |
| NRS Score Three Weeks After Injection | 3 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 2 |
| 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 | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Injection Visit | Lost to Follow-up | 1 | 0 |
| Second Injection Visit | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Botox Then Placebo | Placebo Then Botox | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Continuous | 48.5 years STANDARD_DEVIATION 7.78 | 49 years STANDARD_DEVIATION 4.24 | 48.75 years STANDARD_DEVIATION 5.12 |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 3 |
| other Total, other adverse events | 0 / 2 | 1 / 3 |
| serious Total, serious adverse events | 0 / 2 | 0 / 3 |
Outcome results
Primary
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.
Time frame: Duration of trial (2-20 months, depending on how long pain relief lasts)
Population: A total of 3 participants completed the study (1 received Placebo first then Botox, 2 received Botox first then Placebo). Each of those 3 participants received both Placebo and Botox, as represented in the overall number of participants analyzed for both treatments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Analgesic Failure | 120.67 days | Standard Deviation 166.79 |
| Botox | Time to Analgesic Failure | 20.67 days | Standard Deviation 22.72 |
Secondary
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.
Time frame: Duration of trial (2-20 months, depending on how long pain relief lasts)
Population: A total of 3 participants completed the study (1 received Placebo first then Botox, 2 received Botox first then Placebo). Each of those 3 participants received both Placebo and Botox, as represented in the overall number of participants analyzed for both treatments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Improvement in Psychosocial Function as Assessed by Outcomes as Dictated by the IMMPACT Guidelines | 12.33 Units on a scale | Standard Deviation 3.79 |
| Botox | Improvement in Psychosocial Function as Assessed by Outcomes as Dictated by the IMMPACT Guidelines | 8 Units on a scale | Standard Deviation 7.21 |
| Botox | Improvement in Psychosocial Function as Assessed by Outcomes as Dictated by the IMMPACT Guidelines | 8 Units on a scale | Standard Deviation 4.36 |
Secondary
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).
Time frame: 3 weeks after injection
Population: A total of 3 participants completed the study (1 received Placebo first then Botox, 2 received Botox first then Placebo). Each of those 3 participants received both Placebo and Botox, as represented in the overall number of participants analyzed for both treatments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | NRS Score Three Weeks After Injection | 3.39 Units on a scale | Standard Deviation 2.46 |
| Botox | NRS Score Three Weeks After Injection | 0.86 Units on a scale | Standard Deviation 0.7 |
| Botox | NRS Score Three Weeks After Injection | 3.2 Units on a scale | Standard Deviation 2.18 |