AmputationTMRNCT05408520
Targeted Muscle Reinnervation Study (TMR)
A study testing Targeted Muscle Reinnervation in people with Amputation, run by University of Arizona at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Amputation
- What is being tested?
- Targeted Muscle Reinnervation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Apr 2022to 25 Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Any individual 18 years and older indicated for a below knee or above knee amputation at Banner-University Medical Center Phoenix
Who cannot join
- Any individual who does not meet inclusion criteria
Trial locations and contacts
1 site in 1 country.
United States1 site
Banner - University Medical Center, Phoenix campus
Phoenix, Arizona, 85006
About this study
Official title: A Randomized Controlled Trial of Targeted Muscle Reinnervation in Patients Requiring Lower Extremity Amputation.
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.
Read the detailed description
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.
- Conditions
- Amputation
- Being tested
- Targeted Muscle Reinnervation
- Keywords
- lower extremity amputation, neuroma, phantom limb pain, nerve damage, postoperative pain amputee, reinnervation, regenerative neurotization
- Medical subject headings
- Neuroma, Phantom Limb
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted Muscle ReinnervationProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Amputation with TMR | Experimental | 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. Receives: Procedure: Targeted Muscle Reinnervation |
| Amputation without TMR (SOC) | No intervention | A traditional amputation follows the normal standard of care, with transection of peripheral nerves. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: Pre-operative through 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2022
- Study start27 Apr 2022
- Primary completion25 Oct 2023
- Study completion25 Oct 2023
Why it stopped: Study not conducted
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for AmputationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joshua Hustedt, MD, MHS, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05408520
- Sponsor's protocol ID
- STUDY00000650
- Acronym
- TMR
- Status last verified
- Jul 2025
- First submitted
- 12 May 2022
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share IPD with other researchers.
Publications
Bowen JB, Ruter D, Wee C, West J, Valerio IL. Targeted Muscle Reinnervation Technique in Below-Knee Amputation. Plast Reconstr Surg. 2019 Jan;143(1):309-312. doi: 10.1097/PRS.0000000000005133.
PubMed 30589808Kuiken TA, Dumanian GA, Lipschutz RD, Miller LA, Stubblefield KA. The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthet Orthot Int. 2004 Dec;28(3):245-53. doi: 10.3109/03093640409167756.
PubMed 15658637Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008 Mar;89(3):422-9. doi: 10.1016/j.apmr.2007.11.005.
PubMed 18295618Bowen JB, Wee CE, Kalik J, Valerio IL. Targeted Muscle Reinnervation to Improve Pain, Prosthetic Tolerance, and Bioprosthetic Outcomes in the Amputee. Adv Wound Care (New Rochelle). 2017 Aug 1;6(8):261-267. doi: 10.1089/wound.2016.0717.
PubMed 28831329Souza JM, Cheesborough JE, Ko JH, Cho MS, Kuiken TA, Dumanian GA. Targeted muscle reinnervation: a novel approach to postamputation neuroma pain. Clin Orthop Relat Res. 2014 Oct;472(10):2984-90. doi: 10.1007/s11999-014-3528-7.
PubMed 24562875Valerio IL, Dumanian GA, Jordan SW, Mioton LM, Bowen JB, West JM, Porter K, Ko JH, Souza JM, Potter BK. Preemptive Treatment of Phantom and Residual Limb Pain with Targeted Muscle Reinnervation at the Time of Major Limb Amputation. J Am Coll Surg. 2019 Mar;228(3):217-226. doi: 10.1016/j.jamcollsurg.2018.12.015. Epub 2019 Jan 8.
PubMed 30634038Valerio I, Schulz SA, West J, Westenberg RF, Eberlin KR. Targeted Muscle Reinnervation Combined with a Vascularized Pedicled Regenerative Peripheral Nerve Interface. Plast Reconstr Surg Glob Open. 2020 Mar 25;8(3):e2689. doi: 10.1097/GOX.0000000000002689. eCollection 2020 Mar.
PubMed 32537346Dumanian GA, Potter BK, Mioton LM, Ko JH, Cheesborough JE, Souza JM, Ertl WJ, Tintle SM, Nanos GP, Valerio IL, Kuiken TA, Apkarian AV, Porter K, Jordan SW. Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees: A Randomized Clinical Trial. Ann Surg. 2019 Aug;270(2):238-246. doi: 10.1097/SLA.0000000000003088.
PubMed 30371518Chang BL, Mondshine J, Attinger CE, Kleiber GM. Targeted Muscle Reinnervation Improves Pain and Ambulation Outcomes in Highly Comorbid Amputees. Plast Reconstr Surg. 2021 Aug 1;148(2):376-386. doi: 10.1097/PRS.0000000000008153.
PubMed 34398088
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Targeted Muscle Reinnervation in Patients Requiring Lower Extremity Amputation.
- ClinicalTrials.gov ID
- NCT05408520
- Acronym / sponsor ID
- TMR / STUDY00000650
- Conditions
- Amputation
- Keywords
- lower extremity amputation, neuroma, phantom limb pain, nerve damage, postoperative pain amputee, reinnervation, regenerative neurotization
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study not conducted
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- 27 Apr 2022 (actual)
- Primary completion
- 25 Oct 2023 (actual)
- Study completion
- 25 Oct 2023 (actual)
- First posted
- 7 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Amputation with TMR | Experimental | Procedure: Targeted Muscle ReinnervationAmputation 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. |
| Amputation without TMR (SOC) | No intervention | –A traditional amputation follows the normal standard of care, with transection of peripheral nerves. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Any individual 18 years and older indicated for a below knee or above knee amputation at Banner-University Medical Center Phoenix
Key exclusion criteria (1 listed)
- Any individual who does not meet inclusion criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Targeted Muscle ReinnervationWhen 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. | Procedure or surgery | Amputation with TMR |
Primary outcome
Effect of TMR on neuroma
Time frame: Pre-operative through 24 months
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).
Effect of TMR on phantom limb pain
Time frame: Pre-operative through 24 months
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).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
- Background: PubMed 30589808Bowen JB, Ruter D, Wee C, West J, Valerio IL. Targeted Muscle Reinnervation Technique in Below-Knee Amputation. Plast Reconstr Surg. 2019 Jan;143(1):309-312. doi: 10.1097/PRS.0000000000005133.
- Background: PubMed 15658637Kuiken TA, Dumanian GA, Lipschutz RD, Miller LA, Stubblefield KA. The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthet Orthot Int. 2004 Dec;28(3):245-53. doi: 10.3109/03093640409167756.
- Background: PubMed 18295618Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008 Mar;89(3):422-9. doi: 10.1016/j.apmr.2007.11.005.
- Background: PubMed 28831329Bowen JB, Wee CE, Kalik J, Valerio IL. Targeted Muscle Reinnervation to Improve Pain, Prosthetic Tolerance, and Bioprosthetic Outcomes in the Amputee. Adv Wound Care (New Rochelle). 2017 Aug 1;6(8):261-267. doi: 10.1089/wound.2016.0717.
- Background: PubMed 24562875Souza JM, Cheesborough JE, Ko JH, Cho MS, Kuiken TA, Dumanian GA. Targeted muscle reinnervation: a novel approach to postamputation neuroma pain. Clin Orthop Relat Res. 2014 Oct;472(10):2984-90. doi: 10.1007/s11999-014-3528-7.
- Background: PubMed 30634038Valerio IL, Dumanian GA, Jordan SW, Mioton LM, Bowen JB, West JM, Porter K, Ko JH, Souza JM, Potter BK. Preemptive Treatment of Phantom and Residual Limb Pain with Targeted Muscle Reinnervation at the Time of Major Limb Amputation. J Am Coll Surg. 2019 Mar;228(3):217-226. doi: 10.1016/j.jamcollsurg.2018.12.015. Epub 2019 Jan 8.
- Background: PubMed 32537346Valerio I, Schulz SA, West J, Westenberg RF, Eberlin KR. Targeted Muscle Reinnervation Combined with a Vascularized Pedicled Regenerative Peripheral Nerve Interface. Plast Reconstr Surg Glob Open. 2020 Mar 25;8(3):e2689. doi: 10.1097/GOX.0000000000002689. eCollection 2020 Mar.
- Background: PubMed 30371518Dumanian GA, Potter BK, Mioton LM, Ko JH, Cheesborough JE, Souza JM, Ertl WJ, Tintle SM, Nanos GP, Valerio IL, Kuiken TA, Apkarian AV, Porter K, Jordan SW. Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees: A Randomized Clinical Trial. Ann Surg. 2019 Aug;270(2):238-246. doi: 10.1097/SLA.0000000000003088.
- Background: PubMed 34398088Chang BL, Mondshine J, Attinger CE, Kleiber GM. Targeted Muscle Reinnervation Improves Pain and Ambulation Outcomes in Highly Comorbid Amputees. Plast Reconstr Surg. 2021 Aug 1;148(2):376-386. doi: 10.1097/PRS.0000000000008153.
- Individual participant dataSharing planned: No. There is no plan to share IPD with other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joshua Hustedt, MD, MHS principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Targeted Muscle Reinnervation in people with Amputation, run by University of Arizona at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of TMR on neuroma (time frame: Pre-operative through 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05408520, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.