Pilot RCT of Efficacy of Perineural Local Anesthetics and Steroids for Chronic Post-traumatic Ankle and Foot Pain

Study Overview
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Brief Summary
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Injections of local anesthetics (freezing) and steroids are often performed around injured nerves in individuals with nerve injury-related pain. The current standard of medical care is to inject a combination of local anesthetics and steroids around injured nerves, but there is no proof that this is better than injecting only local anesthetic, or even just sterile salt water. There is evidence to believe that injection of local anesthetic (without the steroid) can calm the injured nerve, and provide pain relief from a few days up to a few months. Injection of sterile salt water also has the potential to provide pain relief by breaking scar tissue around the nerve, thereby relieving compression. The aim of this study is to compare pain relief and possible adverse effects from these three different treatments for foot and ankle nerve pain relief. All 30 participants will be recruited over 9 months from the Altum Health clinic at Toronto Western Hospital. 10 participants will be randomly assigned to each treatment. Each patient will receive 3 injections over 3 weeks or so. Participants will have an in-clinic follow-up at 1 month after the last injection, and a phone follow-up 3 months after the last injection. This is a small-scale study, and information obtained from this study will help in planning and conduct of a larger study with more participants. The larger study will help determine the best possible option for injection in patients with nerve-related injury pain.

Official Title
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A Pilot Randomized Controlled Trial of Efficacy of Perineural Local Anesthetics and Steroids for Chronic Post-traumatic Neuropathic Pain in the Ankle and the Foot: The PREPLAN Study

Conditions
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CHRONIC POST-TRAUMATIC NEUROPATHIC PAIN IN ANKLE AND FOOT

Intervention / Treatment
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* Drug: 0.9% saline
* Drug: 0.25% bupivacaine hydrochloride injectable suspension USP
* Drug: 4mg/cc methylprednisolone acetate injectable suspension USP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pain in foot in neuro-anatomically congruent location following trauma (including surgery) for more than three months Physician-reported DN4 scoring confirming neuropathic pain (score > 3/10) Average intensity of pain more than 3/10 on numerical rating score Failed trial of appropriate doses of first line medications for neuropathic pain (anticonvulsants and/or antidepressants) for six weeks Exclusion Criteria: Age < 18 or age ≥ 80 years Perineural or intra-articular steroid injections in the last 6 months Allergy to local anesthetics and/or steroids Ongoing litigation issues related to the patient's pain Pregnancy Coagulopathy or systemic infection Peripheral neuropathy or myopathy, central neuropathic pain (e.g. post-stroke pain) Infection in the ankle or foot An unstable medical or psychiatric condition Significant catastrophizing as indicated by pain catastrophizing scale (PCS) score equal to or more than 30/52

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 0.9% saline (salt water)<br>0.5mL 0.25% bupivacaine subcutaneous injection, 2-6cc 0.9% saline injection per nerve (20cc max) | Drug: 0.9% saline<br> <br> * Other names: Salt Water;|
| Active Comparator: local anesthetic (freezing)<br>0.5mL 0.25% bupivacaine subcutaneous injection, 2-6cc 0.25% bupivacaine per nerve (20cc max) | Drug: 0.25% bupivacaine hydrochloride injectable suspension USP<br> <br> * Other names: Marcaine;|
| Active Comparator: local anesthetic (freezing) and steroid<br>0.5mL 0.25% bupivacaine subcutaneous injection, 2-6cc 0.25% bupivacaine and 4mg/cc methylprednisolone per nerve (20cc max) | Drug: 0.25% bupivacaine hydrochloride injectable suspension USP<br> <br> * Other names: Marcaine;Drug: 4mg/cc methylprednisolone acetate injectable suspension USP<br> <br> * Other names: Depo-Medrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enrollment and retention of participants (SEE DESCRIPTION) | Factors considered in assessment: Enrolling at least 75% of eligible patients, enrolling at least 9 patients monthly, retention till study end of at least 90% of participants | At end of study (1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central tendency (mean) and spread (standard deviation) of Numerical Rating Score (NRS) ratings of Foot and Ankle pain |  | At 1-month and 3-months post-intervention | 
| Change in scores of Pain Catastrophizing Score (PCS) |  | Baseline and at 1-month post-intervention | 
| Change in scores of Dolores Neuropathique (DN4) |  | Baseline and at 1-month post-intervention | 
| Change in scores of Neuropathic Pain Symptom Inventory (NPSI) |  | Baseline and at 1-month post-intervention | 
| Change in scores of anxiety component scores on the Hospital Anxiety and Depression Scale (HADS) |  | Baseline and at 1-month post-intervention | 
| Change in scores of depression scores on the Patient Health Questionnaire-9 (PHQ-9) |  | Baseline and at 1-month post-intervention | 
| Change in scores of Brief Pain Inventory interference with activities (BPI-I) |  | Baseline and at 1-month post-intervention | 
| Change in scores of Short Form-12 (SF-12) |  | Baseline and at 1-month post-intervention | 
| Change in scores of Lower Extremity Function Score (LEFS) |  | Baseline and at 1-month post-intervention | 
| Evaluate the impact of study interventions on requirement for opioids (measured as average daily oral morphine equivalents in mg) and neuropathic medications (average daily doses of gabapentin and/or amitriptyline in mg) |  | At end of study (1 year) | 
| Change in pre- and post-intervention levels of blood glucose and blood pressure |  | Baseline and at 1-month post-intervention | 
| Measure incidence of infections at the injection site, skin discoloration or atrophy at the injection site, fractures, and evidence of myopathy |  | Baseline and at 1-month post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ankle pain, foot pain, methylprednisolone, neuropathic pain