Effect of Prophylactic TMR and RPNI on Neuroma and Phantom Limb Pain

Study Overview
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Brief Summary
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The purpose of this study is to analyze the efficacy of novel interventions in post-amputation surgical care (specifically Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interface) on post-amputation pain and functional outcomes at the time of amputation. These novel interventions have been shown to be successful in treating the downstream effects of amputations (pain, phantom limb pain, neuroma pain, etc.), but has not been studied in a randomized manner at the time of amputation.

Detailed Description
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The investigators plan a randomized control trial of all eligible patients undergoing major limb amputation at Parkland Memorial Hospital. Eligible patients undergoing an amputation will be consented for all possible interventions and randomized to either receive Targeted Muscle Re-Innervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), or standard post-amputation surgical care at the time of their operation. Key pre-operative data including patient sex, age, BMI, past medical history, past surgical history, medications, allergies, social history, social support systems, exposure to narcotic medication, and reason for amputation will be analyzed. Intra-operatively, patients randomized to the treatment arm will receive TMR or RPNI and the transected nerve ends addressed will be recorded. Post-operative data that will be recorded include hospital stay, complications related to the procedure, complications leading to reoperation, functional results, need for pain medication, incidence of phantom limb pain, incidence of painful neuromas, length of follow-up, and all adverse events/complications. Analyses will be conducted using data obtained from patient medical records from the Parkland Health & Hospital System.

Official Title
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Prophylactic Treatment of Neuroma and Phantom Limb Pain With Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Interface (RPNI) at the Time of Major Limb Amputation: A Randomized Control Trial

Conditions
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Amputation, Neuroma Amputation, Phantom Limb Pain, Residual Limbs

Intervention / Treatment
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* Procedure: Targeted Muscle Re-innervation
* Procedure: Regenerative Peripheral Nerve Interface
* Procedure: Standard Post-Amputation Surgical Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years old Patients scheduled for amputation of upper or lower extremity (including digit, ray, and hand) as a primary or secondary sequela of trauma. Patients scheduled for amputation of upper or lower extremity (including digit, ray, and hand) for primary or secondary sequelae of malignancy. Secondary sequalae include but is not limited to metastatic disease and osteolytic disease. Patients scheduled for amputation of upper or lower extremity (including digit, ray, and hand) for vasculitic diseases. Exclusion Criteria: Patients less than 18 years old Patients with cognitive impairment Patients who are imprisoned at the time of randomization Patients currently enrolled in other studies relating to neuropathic pain Patients actively undergoing radiation therapy Patients with existing neuroma or underwent prior neuroma surgery Patients with amputations scheduled congenital reasons

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Arm<br>Standard Post-Amputation Surgical Care: Briefly, the transected nerves will be blindly tucked into surrounding bulky soft tissue to protect the nerve ends before the wound is closed. | Procedure: Standard Post-Amputation Surgical Care<br>* Standard post-amputation surgical care involves placing transected nerve ends into muscle/soft tissue proximal to the site of amputation.<br>|
| Experimental: Targeted Muscle Re-innervation<br>Briefly, each transected nerve is identified after amputation using 6-0 Prolene suture and is dissected proximally for length. With minimal dissection, a nerve stimulator is used to identify functional motor nerve branches. Near the point where the motor branch enters the muscle, the motor nerve branch is transected and an end-to-end coaptation is performed with a nearby tagged amputated nerve. | Procedure: Targeted Muscle Re-innervation<br>* Targeted Muscle Re-innervation involves re-routing transected nerve ends to functional motor nerves proximal to the site of amputation.<br>|
| Experimental: Regenerative Peripheral Nerve Interface<br>Briefly, a muscle graft (usually from the amputated limb) is wrapped around the clean ends of the transected nerve(s). | Procedure: Regenerative Peripheral Nerve Interface<br>* Regenerative Peripheral Nerve Interface involves placing transected nerve ends in harvested muscle grafts.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Phantom Limb Pain | The primary outcome measure of the study will the incidence of phantom limb pain in each group over the course of the recovery period. | Specifically at the time point 1 year after their primary incisions have healed. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity score as measured PROMIS (Patient Reported Outcomes Measurement Information System) score | Pain intensity score is measured bv PROMIS (Patient Reported Outcomes Measurement Information System) Scores via patient questionnaires administered at follow-up visits. Possible scores range from 1-5 where higher scores indicate worse outcome (pain severity). | Until 2 years after incisions have healed. | 
| Pain interference score as measured by PROMIS (Patient Reported Outcomes Measurement information System) questionnaire | Pain interference score as measured by PROMIS (Patient Reported Outcomes Measurement information System) scores via patient questionnaires administered at follow-up visits. Possible scores range from 1-5, where higher scores indicate worse outcome (pain interference). | Until 2 years after incisions have healed. | 
| Pain behavior measured by PROMIS (Patient Reported Outcomes Measurement Information System) questionnaire | Pain behavior score measured by PROMIS (Patient Reported Outcomes Measurement Information System) questionnaire that pertains to subject social health. Raw summed score from 8 to 40, where 40 represents severely maladaptive pain behavior. | Until 2 years after incisions have healed. | 
| Narcotic medical use post-operatively as measured by MME (Morphine Milligram Equivalent) Score | Narcotic medical use post-operatively as measured by MME (Morphine Milligram Equivalent) Score This is a tool to condense and standardize the patient's narcotic pain regimen. | Until 2 years after incisions have healed. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Targeted Muscle Re-innervation, Regenerative Peripheral Nerve Interface, TMR, RPNI