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
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 A
Subcutaneous injection of Botulinum Toxin Type A into the patient's scar tissue
DRUGPlacebo - Saline
Subcutaneous Saline injection given at site of scar neuroma
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Until Analgesic Failure | Each participant was assessed for up to 224 days per intervention (injection) or until they returned to NRS baseline | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NRS Score Three Weeks After Injection | Three weeks after injection | The NRS scores range from 0-100, where 0 indicated no pain and 100 indicated the worst pain. |
Countries
United States
Participant flow
Pre-assignment details
84 total participants were enrolled. 46 were withdrawn before randomization due to failure at screening or following protocol. A total of 38 participants were randomized. A total of 30 participants remained for the first injection after 8 were withdrawn due to medication, surgery, or patient decision. A total of 27 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Then Botox Placebo - Saline:
Subcutaneous Saline injection given at site of scar neuroma
Botulinum Toxin A:
Subcutaneous injection of Botulinum Toxin Type A into the patient's scar tissue | 13 |
| Botox Then Placebo Botulinum Toxin A:
Subcutaneous injection of Botulinum Toxin Type A into the patient's scar tissue
Placebo - Saline:
Subcutaneous Saline injection given at site of scar neuroma | 14 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout (28 Days) | Protocol Violation | 0 | 1 |
| Washout (28 Days) | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Botox Then Placebo | Placebo Then Botox | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 11 Participants | 23 Participants |
| Age, Continuous | 50.14 Years STANDARD_DEVIATION 12.48 | 46.62 Years STANDARD_DEVIATION 14.87 | 48.44 Years STANDARD_DEVIATION 13.54 |
| Region of Enrollment United States | 14 participants | 13 participants | 27 participants |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 |
| other Total, other adverse events | 8 / 13 | 10 / 14 |
| serious Total, serious adverse events | 0 / 13 | 0 / 14 |
Outcome results
Primary
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
Time frame: Each participant was assessed for up to 224 days per intervention (injection) or until they returned to NRS baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time Until Analgesic Failure | 76.3 Days | Standard Deviation 86.82 |
| Botox | Time Until Analgesic Failure | 79 Days | Standard Deviation 92.12 |
Secondary
NRS Score Three Weeks After Injection
The NRS scores range from 0-100, where 0 indicated no pain and 100 indicated the worst pain.
Time frame: Three weeks after injection
Population: Although 27 participants completed the study, 3 participants were excluded from analysis of the NRS score because they had missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | NRS Score Three Weeks After Injection | 35.5 Units on a scale | Standard Deviation 20.07 |
| Botox | NRS Score Three Weeks After Injection | 34.7 Units on a scale | Standard Deviation 23.38 |