AmputationNCT05344261
Effect of Prophylactic TMR and RPNI on Neuroma and Phantom Limb Pain
A study testing Targeted Muscle Re-innervation, Regenerative Peripheral Nerve Interface and Standard Post-Amputation Surgical Care in people with Amputation and Neuroma Amputation, run by University of Texas Southwestern Medical Center.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Amputation, Neuroma Amputation, Phantom Limb Pain
- What is being tested?
- Targeted Muscle Re-innervation, Regenerative Peripheral Nerve Interface and Standard Post-Amputation Surgical Care
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2023to 30 Dec 2024
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Amputation, Neuroma Amputation, Phantom Limb Pain, Residual Limbs
- Being tested
- Targeted Muscle Re-innervation, Regenerative Peripheral Nerve Interface, Standard Post-Amputation Surgical Care
- Keywords
- Targeted Muscle Re-innervation, Regenerative Peripheral Nerve Interface, TMR, RPNI
- Medical subject headings
- Phantom Limb
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted Muscle Re-innervationProcedure or surgery
Targeted Muscle Re-innervation involves re-routing transected nerve ends to functional motor nerves proximal to the site of amputation.
Regenerative Peripheral Nerve InterfaceProcedure or surgery
Regenerative Peripheral Nerve Interface involves placing transected nerve ends in harvested muscle grafts.
Standard Post-Amputation Surgical CareProcedure or surgery
Standard post-amputation surgical care involves placing transected nerve ends into muscle/soft tissue proximal to the site of amputation.
| Study group | Role | What they receive |
|---|---|---|
| Control Arm | Active comparator | 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. Receives: Procedure: Standard Post-Amputation Surgical Care |
| Targeted Muscle Re-innervation | Experimental | 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. Receives: Procedure: Targeted Muscle Re-innervation |
| Regenerative Peripheral Nerve Interface | Experimental | Briefly, a muscle graft (usually from the amputated limb) is wrapped around the clean ends of the transected nerve(s). Receives: Procedure: Regenerative Peripheral Nerve Interface |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Specifically at the time point 1 year after their primary incisions have healed.
Secondary outcomes (4)
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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Until 2 years after incisions have healed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2022
- Study start1 Mar 2023 (estimated)
- Primary completion30 Dec 2024 (estimated)
- Study completion30 Dec 2024 (estimated)
Why it stopped: study never initiated and no participants enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for AmputationStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- 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
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Travis Boyd, University of Texas Southwestern Medical Center
- Investigators
- Deborah Noble, Study director, UT Southwestern Department of Plastic Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05344261
- Sponsor's protocol ID
- STU-2021-0348
- Status last verified
- Nov 2023
- First submitted
- 28 Mar 2022
- Last updated
- 5 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ziegler-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 18295618Dumanian 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 30371518Valerio 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 30634038Eberlin KR, Ducic I. Surgical Algorithm for Neuroma Management: A Changing Treatment Paradigm. Plast Reconstr Surg Glob Open. 2018 Oct 16;6(10):e1952. doi: 10.1097/GOX.0000000000001952. eCollection 2018 Oct.
PubMed 30534497Kubiak CA, Kemp SWP, Cederna PS, Kung TA. Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain. Plast Reconstr Surg. 2019 Sep;144(3):421e-430e. doi: 10.1097/PRS.0000000000005922.
PubMed 31461024Santosa KB, Oliver JD, Cederna PS, Kung TA. Regenerative Peripheral Nerve Interfaces for Prevention and Management of Neuromas. Clin Plast Surg. 2020 Apr;47(2):311-321. doi: 10.1016/j.cps.2020.01.004. Epub 2020 Feb 1.
PubMed 32115057Kuiken TA, Barlow AK, Hargrove L, Dumanian GA. Targeted Muscle Reinnervation for the Upper and Lower Extremity. Tech Orthop. 2017 Jun;32(2):109-116. doi: 10.1097/BTO.0000000000000194.
PubMed 28579692
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05344261
- Acronym / sponsor ID
- STU-2021-0348
- Conditions
- Amputation, Neuroma Amputation, Phantom Limb Pain, Residual Limbs
- Keywords
- Targeted Muscle Re-innervation, Regenerative Peripheral Nerve Interface, TMR, RPNI
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: study never initiated and no participants enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2023 (estimated)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 30 Dec 2024 (estimated)
- First posted
- 25 Apr 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 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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control Arm | Active comparator | Procedure: Standard Post-Amputation Surgical CareStandard 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. |
| Targeted Muscle Re-innervation | Experimental | Procedure: Targeted Muscle Re-innervationBriefly, 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. |
| Regenerative Peripheral Nerve Interface | Experimental | Procedure: Regenerative Peripheral Nerve InterfaceBriefly, a muscle graft (usually from the amputated limb) is wrapped around the clean ends of the transected nerve(s). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
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 Re-innervationTargeted Muscle Re-innervation involves re-routing transected nerve ends to functional motor nerves proximal to the site of amputation. | Procedure or surgery | Targeted Muscle Re-innervation |
| Regenerative Peripheral Nerve InterfaceRegenerative Peripheral Nerve Interface involves placing transected nerve ends in harvested muscle grafts. | Procedure or surgery | Regenerative Peripheral Nerve Interface |
| Standard Post-Amputation Surgical CareStandard post-amputation surgical care involves placing transected nerve ends into muscle/soft tissue proximal to the site of amputation. | Procedure or surgery | Control Arm |
Primary outcome
Incidence of Phantom Limb Pain
Time frame: Specifically at the time point 1 year after their primary incisions have healed.
The primary outcome measure of the study will the incidence of phantom limb pain in each group over the course of the recovery period.
4 secondary outcomes
Pain intensity score as measured PROMIS (Patient Reported Outcomes Measurement Information System) score
Time frame: Until 2 years after incisions have healed.
Pain interference score as measured by PROMIS (Patient Reported Outcomes Measurement information System) questionnaire
Time frame: Until 2 years after incisions have healed.
Pain behavior measured by PROMIS (Patient Reported Outcomes Measurement Information System) questionnaire
Time frame: Until 2 years after incisions have healed.
Narcotic medical use post-operatively as measured by MME (Morphine Milligram Equivalent) Score
Time frame: Until 2 years after incisions have healed.
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 5 Dec 2023.
- 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 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 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 30534497Eberlin KR, Ducic I. Surgical Algorithm for Neuroma Management: A Changing Treatment Paradigm. Plast Reconstr Surg Glob Open. 2018 Oct 16;6(10):e1952. doi: 10.1097/GOX.0000000000001952. eCollection 2018 Oct.
- Background: PubMed 31461024Kubiak CA, Kemp SWP, Cederna PS, Kung TA. Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain. Plast Reconstr Surg. 2019 Sep;144(3):421e-430e. doi: 10.1097/PRS.0000000000005922.
- Background: PubMed 32115057Santosa KB, Oliver JD, Cederna PS, Kung TA. Regenerative Peripheral Nerve Interfaces for Prevention and Management of Neuromas. Clin Plast Surg. 2020 Apr;47(2):311-321. doi: 10.1016/j.cps.2020.01.004. Epub 2020 Feb 1.
- Background: PubMed 28579692Kuiken TA, Barlow AK, Hargrove L, Dumanian GA. Targeted Muscle Reinnervation for the Upper and Lower Extremity. Tech Orthop. 2017 Jun;32(2):109-116. doi: 10.1097/BTO.0000000000000194.
- Individual participant dataSharing planned: No
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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.
Deborah Noble study director
UT Southwestern Department of Plastic Surgery
Questions about this trial
What is this clinical trial studying?
A study testing Targeted Muscle Re-innervation, Regenerative Peripheral Nerve Interface and Standard Post-Amputation Surgical Care in people with Amputation and Neuroma Amputation, run by University of Texas Southwestern Medical Center.
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 5 inclusion and 7 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 5 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
Incidence of Phantom Limb Pain (time frame: Specifically at the time point 1 year after their primary incisions have healed.). 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 NCT05344261, which also lists 7 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 5 Dec 2023.