Targeted Muscle Reinnervation Study (TMR)

Study Overview
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Brief Summary
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The purpose of this study is to examine the effect of targeted muscle reinnervation on the outcomes of amputees at a level 1 trauma center. The investigators propose to randomize all patients requiring amputation with and without targeted muscle reinnervation. This study will help delineate the efficacy of targeted muscle reinnervation in the general population.

Detailed Description
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After an amputation, patients often experience pain, both from the cut nerves themselves as well as perceived pain from a 'missing' limb. A technique has been developed to regenerate the cut nerve so that it doesn't cause pain. The technique includes sewing the nerve into another nerve so that it continues to function. This technique, called targeted muscle reinnervation, can reduce the postoperative pain amputee patients experience. Targeted muscle reinnervation (TMR) has shown promising success in the reduction of neuroma and phantom limb pain following extremity amputation. TMR was originally designed to allow for regenerative neurotization of end target muscle for the purpose of utilizing myoelectric prosthesis for amputees. While these indications have been successful, it has been the secondary outcome of reduction in neuroma and phantom limb pain that have led to significant improvements in patient outcomes. In the United States there are 200,000 amputations every year, and 1.6 million Americans living as amputees. Despite the technical success of the procedures, over 75% of patients will experience neuroma pain, and 85% will experience phantom limb pain. In addition, this pain limits the postoperative ambulation of many patients leading to a 75% 5-year mortality rate for patients who undergo lower extremity amputation in the US.3 TMR has shown promising clinical results in addressing phantom limb and neuroma pain. In pooled data it showed that patients who underwent TMR had residual limb pain of 0% and phantom limb pain of 7%. In a larger comparative study of 489 patients, patients who underwent TMR had phantom limb pain scores with an average of 1, compared to an average of 5 for control amputees. The TMR patients also had an average residual limb pain of 1, compared to an average of 4 for controls. Yet despite these promising outcomes, questions with TMR still remain. In the Valerio study, the largest study to date, all patients were grouped together regardless of the reason for amputation. While the percentage of patients undergoing amputation for cancer, infection, ischemia, trauma, or other, was reported, there was no comparison of outcomes in these groups. In a new study, the benefits of TMR have been shown to hold in highly comorbid patients presenting to a level 1 trauma center. Given the outcomes of TMR in these studies, there seems to be strong evidence to encourage the procedure, yet no study has yet to randomize patients to measure the true clinical outcome in a trauma population.

Official Title
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A Randomized Controlled Trial of Targeted Muscle Reinnervation in Patients Requiring Lower Extremity Amputation.

Conditions
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Amputation

Intervention / Treatment
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* Procedure: Targeted Muscle Reinnervation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any individual 18 years and older indicated for a below knee or above knee amputation at Banner-University Medical Center Phoenix Exclusion Criteria: Any individual who does not meet inclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Interventional Model Description: A traditional amputation follows the normal standard of care, with transection of peripheral nerves. The TMR procedure will transfer the transected nerves to adjacent muscle nerves.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amputation with TMR<br>Amputation will follow standard procedure, but with the addition of the TMR procedure, which involves rerouting severed or injured nerves to new muscle targets using microsurgical techniques to provide the nerve endings with a new muscle to innervate. | Procedure: Targeted Muscle Reinnervation<br>* When a nerve is severed or injured, it attempts to regenerate. The TMR procedure will transfer the transected nerves to adjacent muscle nerves in efforts to encourage the nerve to regenerate in an organized fashion.<br>|
| No Intervention: Amputation without TMR (SOC)<br>A traditional amputation follows the normal standard of care, with transection of peripheral nerves. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of TMR on neuroma | Subject data will be collected from EMR and patient reported outcome surveys, rating pain on a scale of 1-10 (1 being no pain and 10 being the worst pain). | Pre-operative through 24 months | 
| Effect of TMR on phantom limb pain | Subject data will be collected from EMR and patient reported outcome surveys, rating pain on a scale of 1-10 (1 being no pain and 10 being the worst pain). | Pre-operative through 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lower extremity amputation, neuroma, phantom limb pain, nerve damage, postoperative pain amputee, reinnervation, regenerative neurotization