Residual Limb PainNCT05009394
Surgical Treatments for Postamputation Pain
A study testing Targeted Muscle Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI) and Standard neuroma treatment, neuroma excision, and muscle burying in people with Residual Limb Pain and Amputation Neuroma, run by Prometei Pain Rehabilitation Center at 9 sites in 7 countries.
Trial summary
This is a double-blind randomised controlled trial (RCT) which compares the effectiveness of three surgical techniques for alleviating residual limb pain (RLP), neuroma pain and phantom limb pain (PLP). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Residual Limb Pain, Amputation Neuroma, Phantom Limb Pain
- What is being tested?
- Targeted Muscle Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI) and Standard neuroma treatment, neuroma excision, and muscle burying
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 9 sitesin 7 countries
- Study dates
- 20 Jun 2023to Jun 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The participant must have a major limb amputation.
- The participant is ≥ 18 years old at the time of consent.
- The participant must be in generally good health to undergo a surgical intervention, as per the clinical investigator's opinion.
- Time since the last amputation must be over a year at the time of consent.
- The participant must have an average residual limb pain score equal or greater than 4 on the Numerical Rating Scale (NRS, 0-10) after the baseline period.
- If the participant has been prescribed pharmacological treatments for pain, there must be no variations in dosage (steady consumption) for at least 1 month before the screening visit.
Show all 9Show fewer
- If the participant has been prescribed non-pharmacological treatments for pain, such as spinal cord stimulation, transcutaneous electrical nerve stimulation, and mirror therapy, the treatment must have ended at least 1 month before the screening visit.
- The participant must have a stable prosthetic fitting for at least a month before the screening visit.
- The participant has a sufficient understanding of the language in which the assessments will be conducted, as per the clinical investigator's opinion.
Who cannot join
- Neurological or other conditions that affect nerve regeneration for the nerve to be treated.
- Active infection in the residual limb.
- Prior RPNI or TMR surgery of the nerve to be treated (with painful neuroma) to address postamputation pain.
- Mental disorders (e.g., schizophrenia, paranoia, psychosis, etc.), reluctance, or language difficulties that result in difficulty understanding the meaning of study participation.
- Ongoing participation in a clinical study that the clinical investigator deems detrimental to participation in this study.
Trial locations and contacts
9 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 7 countries
United States3 sites, 3 recruiting
- Not yet recruiting
University of Michigan Health System
Ann Arbor, Michigan, 48109
Paul Cederna, MD, PhD, cederna@med.umich.edu
Paul Cederna, MD, PhD
- Not yet recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Ian Valerio, MD, PhD, IVALERIO@mgh.harvard.edu
Ian Valerio, MD, PhD
- Not yet recruiting
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Jason Ko, MD, PhD, jason.ko@nm.org
Jason Ko, MD, PhD
Australia1 site, 1 recruiting
- Not yet recruiting
Dandenong Hospital, Monash Health
Melbourne
Michael Lo, MD, PhD, mlo@bigpond.net.au
Michael Lo, MD, PhD
Canada1 site, 1 recruiting
- Not yet recruiting
University of Alberta Hospital
Edmonton, Alberta, AB T6G 2B7
Adil Ladak, MD, PhD, aladak@ualberta.ca
Adil Ladak, MD, PhD
Chile1 site, 1 recruiting
- Not yet recruiting
Worker Hospital
Santiago
Juan Manuel Breyer, MD, PhD, jmbreyer@hotmail.com
Juan Manuel Breyer, MD, PhD
Italy1 site, 1 recruiting
- Recruiting
Rizzoli Orthopedic Institute
Bologna, Emilia-Romagna, 40136
Paolo Sassu, MD, PhD, sassupaolo@gmail.com
Paolo Sassu, MD, PhD
Sweden1 site, 1 recruiting
- Not yet recruiting
Sahlgrenska University Hospital
Mölndal, Västra Götaland County, 431 80
Emily Pettersen, MSc, emily-pettersen@outlook.com
Carina Reinholdt, MD, PhD
United Kingdom1 site, 1 recruiting
- Not yet recruiting
NHS Lothian, NHS Clyde & Greater Glasgow, and NHS Grampian
Edinburgh
Aidan Roche, MD, PhD, aidan.roche@ed.ac.uk
Aidan Roche, MD, PhD
About this study
This is a double-blind randomised controlled trial (RCT) which compares the effectiveness of three surgical techniques for alleviating residual limb pain (RLP), neuroma pain and phantom limb pain (PLP). The three surgical treatments are Targeted Muscles Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), and an active control (neuroma excision and muscle burying). Patients will be follow-up for 4 years.
Read the detailed description
Residual limb pain (RLP), neuroma pain, and phantom limb pain (PLP) can develop after the loss of a body part and fall within the umbrella term postamputation pain. However, the underlaying causes to postamputation pain are diverse and must be addressed accordingly. Surgical treatments for RLP have become a popular approach and have shown great potential for successful outcomes. The two surgical interventions, Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI), are globally used in pain management therapies.
This is a multi-centre, double-blind, superiority RCT which takes place at 9 hospitals in 7 countries:the Sahlgrenska University Hospital in Gothenburg, Sweden; the Rizzoli Orthopaedic Institute in Bologna, Italy; the University of Alberta Hospital in Edmonton, Canada; Worker Hospital in Santiago, Chile; the NHS Lothian, NHS Clyde \& Greater Glasgow, and NHS Grampian, UK; Dandenong Hospital, Monash Health in Melbourne, Australia; the Northwestern Memorial Hospital in Chicago, USA; the University of Michigan Health System in Ann Arbor, Michigan, USA; and within the Massachusetts General Hospital in Boston, USA. One hundred ten participants will be recruited and randomly assigned to one of three surgical treatments (TMR, RPNI, or control) in an equal allocation ratio (n = 37 per group). Each participant will be followed up short term (1, 3, 6, and 12 months post-surgery) and long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participants are unsatisfied with the outcome of the treatment, they may request one of the other treatments. In such a case, a medical evaluation and further treatment options will be discussed in consultation with the clinical investigator at the site.
The study design is chosen to be able to follow RLP, neuroma pain and PLP intensity before and after surgical treatment as well as to investigate how pain develops up to four years post-surgery. The evaluation methods in the study are based on previously used methods in the literature for RLP-, neuroma- and PLP-related pain research. The questionnaires are previously used in clinical settings.
- Being tested
- Targeted Muscle Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), Standard neuroma treatment, neuroma excision, and muscle burying
- Medical subject headings
- Phantom Limb, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted Muscle Reinnervation (TMR)Procedure or surgery
Surgical procedure used to rewire injured proximal nerves to motor nerves directly innervating an otherwise redundant target muscle.
Regenerative Peripheral Nerve Interface (RPNI)Procedure or surgery
Surgical procedure where the the nerve is split into fascicles and wrapped in free muscle grafts.
Standard neuroma treatment, neuroma excision, and muscle buryingProcedure or surgery
Surgical procedure where the neuroma is excised and the nerve stump is buried in an adjacent deep muscle.
| Study group | Role | What they receive |
|---|---|---|
| Targeted Muscle Reinnervation (TMR) | Active comparator | The surgical procedure comprises three steps: preparation of the donor nerve, identification of a motor branch to the targeted muscle, and nerve coaptation. To prepare the donor nerve, the surgeon will identify the nerve with a painful neuroma and resect the neuroma up to healthy fascicles. Next, the surgeon will identify a motor branch to a nearby target muscle and will confirm muscle contraction using a hand-held nerve stimulator. The motor branch to the target muscle will be transected as close as possible to its entry point without tension. In the final step, the previous nerve stump from which the neuroma was resected will be transferred and coapted to the newly severed motor branch that innervates the target muscle and secured by 2-3 non-resorbable monofilament sutures. The surgery time is approximately 2-3 hours and it takes place in the hospital. Receives: Procedure: Targeted Muscle Reinnervation (TMR) |
| Regenerative Peripheral Nerve Interface (RPNI) | Active comparator | The RPNI procedure involves construction of a residual peripheral nerve split into several nerve fascicles and implanted into free skeletal muscle grafts. First, the surgeon identifies the nerve with a painful neuroma and resect the neuroma up to healthy fascicles. Then, a longitudinal intraneural dissection will be performed exposing its fascicles. Next, autologous muscle grafts will be harvested from a healthy donor site, and the dissected nerve stumps will be placed parallel to the muscle fibers. The nerve stump will be secured to the muscle graft, thereafter the graft will be wrapped around the nerve stump and anchored in the folded graft, thus creating an RPNI. This will be repeated for each fascicle obtained from splitting the transected nerve. Lastly, the RPNIs will be placed in a protected area. The surgery time is approximately 2-3 hours and it takes place in the hospital. Receives: Procedure: Regenerative Peripheral Nerve Interface (RPNI) |
| Standard neuroma treatment, neuroma excision, and muscle burying | Active comparator | The standard neuroma treatment, also called neuroma transposition, includes excision of the terminal neuroma and burying the nerve into an adjacent deep muscle.The standard neuroma treatment entails the excision of the terminal neuroma and then implanting the nerve into an adjacent muscle. Firstly, the surgeon will identify the nerve with a painful neuroma and thereafter resect the neuroma up to healthy fascicles. Next, the surgeon will identify a nearby muscle which is not involved in joint motion and has limited output opportunities for the nerve. The nerve will then be channeled at least 1 cm inside the muscle without applying any tension to it and secured by 1-2 non-resorbable monofilament sutures. The identified nerve with the painful neuroma will not be treated with any additional therapy than the resection (e.g., diathermy, pharmacotherapy, crushing, etc.). The surgery time is approximately 1-2 hours and it takes place in the hospital. Receives: Procedure: Standard neuroma treatment, neuroma excision, and muscle burying |
What is being measured
The primary outcome is the main question the study is designed to answer.
Residual limb pain intensity
Difference in residual limb pain intensity will be measured by numerical rating scale (NRS, 0-10), where 0 - no pain and 10 - worst imaginable pain, between baseline period and at the 12-month follow-up visit.
Measured: Baseline to 12-month post-surgery
Secondary outcomes (2)
Neuroma pain intensity
Difference in neuroma pain intensity will be measured by numerical rating scale (NRS, 0-10), where 0 - no pain and 10 - worst imaginable pain, between baseline period and at the 12-month follow-up visit.
Measured: Baseline to 12-month post-surgery
Phantom limb pain intensity
Difference in phantom limb pain intensity will be measured by numerical rating scale (NRS, 0-10), where 0 - no pain and 10 - worst imaginable pain, between baseline period and at the 12-months follow-up visit.
Measured: Baseline to12-month post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2021
- Study start20 Jun 2023
- Primary completionJun 2026 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Residual Limb PainStudies 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
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prometei Pain Rehabilitation Center
- Sponsor type
- University, hospital or other
- Collaborators
- Vastra Gotaland Region, Göteborg University, Istituto Ortopedico Rizzoli, Hospital del Trabajador de Santiago, NHS Lothian, NHS Greater Clyde and Glasgow, NHS Grampian, Northwestern Memorial Hospital, University of Michigan, Massachusetts General Hospital, Dandenong Hospital, University of Alberta
- Responsible party
- Principal investigator, Max Ortiz Catalan, Prometei Pain Rehabilitation Center
- Investigators
- Max Ortiz Catalan, PhD, Principal investigator, Prometei Pain Rehabilitation Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05009394
- Sponsor's protocol ID
- 2021-02346
- Status last verified
- Jan 2025
- First submitted
- 12 Jul 2021
- Last updated
- 9 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dumanian 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 30371518Souza 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 24562875Woo SL, Kung TA, Brown DL, Leonard JA, Kelly BM, Cederna PS. Regenerative Peripheral Nerve Interfaces for the Treatment of Postamputation Neuroma Pain: A Pilot Study. Plast Reconstr Surg Glob Open. 2016 Dec 27;4(12):e1038. doi: 10.1097/GOX.0000000000001038. eCollection 2016 Dec.
PubMed 28293490Pettersen E, Sassu P, Reinholdt C, Dahm P, Rolfson O, Bjorkman A, Innocenti M, Pedrini FA, Breyer JM, Roche A, Hart A, Harrington L, Ladak A, Power H, Hebert J, Ortiz-Catalan M. Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial. Trials. 2023 May 2;24(1):304. doi: 10.1186/s13063-023-07286-0.
PubMed 37131180Chang 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 34398088Bjorklund KA, Alexander J, Tulchin-Francis K, Yanes NS, Singh S, Valerio I, Klingele K, Scharschmidt T. Targeted Muscle Reinnervation for Limb Amputation to Avoid Neuroma and Phantom Limb Pain in Patients Treated at a Pediatric Hospital. Plast Reconstr Surg Glob Open. 2023 Apr 13;11(4):e4944. doi: 10.1097/GOX.0000000000004944. eCollection 2023 Apr.
PubMed 37063502Kubiak 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 31461024Valerio 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 30634038Pettersen E, Sassu P, Pedrini FA, Granberg H, Reinholdt C, Breyer JM, Roche A, Hart A, Ladak A, Power HA, Leung M, Lo M, Valerio I, Eberlin KR, Ko J, Dumanian GA, Kung TA, Cederna P, Ortiz-Catalan M. Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain. J Vis Exp. 2024 Mar 15;(205). doi: 10.3791/66378.
PubMed 38557950Pettersen E, Sassu P, Pedrini FA, Granberg H, Reinholdt C, Breyer JM, Roche A, Hart A, Ladak A, Power HA, Leung M, Lo M, Valerio I, Eberlin KR, Kung TA, Cederna P, Souza JM, Aszmann O, Ko J, Dumanian GA, Ortiz-Catalan M. Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain. J Vis Exp. 2024 Mar 8;(205). doi: 10.3791/66379.
PubMed 38526122
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surgical Treatments for Postamputation Pain
- ClinicalTrials.gov ID
- NCT05009394
- Acronym / sponsor ID
- 2021-02346
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Prometei Pain Rehabilitation CenterUniversity, hospital or other
- Collaborators
- Vastra Gotaland Region, Göteborg University, Istituto Ortopedico Rizzoli, Hospital del Trabajador de Santiago, NHS Lothian, NHS Greater Clyde and Glasgow, NHS Grampian, Northwestern Memorial Hospital, University of Michigan, Massachusetts General Hospital, Dandenong Hospital, University of Alberta
- Study start
- 20 Jun 2023 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 17 Aug 2021 (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.
This is a double-blind randomised controlled trial (RCT) which compares the effectiveness of three surgical techniques for alleviating residual limb pain (RLP), neuroma pain and phantom limb pain (PLP). The three surgical treatments are Targeted Muscles Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), and an active control (neuroma excision and muscle burying). Patients will be follow-up for 4 years.
Detailed description
Residual limb pain (RLP), neuroma pain, and phantom limb pain (PLP) can develop after the loss of a body part and fall within the umbrella term postamputation pain. However, the underlaying causes to postamputation pain are diverse and must be addressed accordingly. Surgical treatments for RLP have become a popular approach and have shown great potential for successful outcomes. The two surgical interventions, Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI), are globally used in pain management therapies.
This is a multi-centre, double-blind, superiority RCT which takes place at 9 hospitals in 7 countries:the Sahlgrenska University Hospital in Gothenburg, Sweden; the Rizzoli Orthopaedic Institute in Bologna, Italy; the University of Alberta Hospital in Edmonton, Canada; Worker Hospital in Santiago, Chile; the NHS Lothian, NHS Clyde \& Greater Glasgow, and NHS Grampian, UK; Dandenong Hospital, Monash Health in Melbourne, Australia; the Northwestern Memorial Hospital in Chicago, USA; the University of Michigan Health System in Ann Arbor, Michigan, USA; and within the Massachusetts General Hospital in Boston, USA. One hundred ten participants will be recruited and randomly assigned to one of three surgical treatments (TMR, RPNI, or control) in an equal allocation ratio (n = 37 per group). Each participant will be followed up short term (1, 3, 6, and 12 months post-surgery) and long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participants are unsatisfied with the outcome of the treatment, they may request one of the other treatments. In such a case, a medical evaluation and further treatment options will be discussed in consultation with the clinical investigator at the site.
The study design is chosen to be able to follow RLP, neuroma pain and PLP intensity before and after surgical treatment as well as to investigate how pain develops up to four years post-surgery. The evaluation methods in the study are based on previously used methods in the literature for RLP-, neuroma- and PLP-related pain research. The questionnaires are previously used in clinical settings.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Targeted Muscle Reinnervation (TMR) | Active comparator | Procedure: Targeted Muscle Reinnervation (TMR)The surgical procedure comprises three steps: preparation of the donor nerve, identification of a motor branch to the targeted muscle, and nerve coaptation. To prepare the donor nerve, the surgeon will identify the nerve with a painful neuroma and resect the neuroma up to healthy fascicles. Next, the surgeon will identify a motor branch to a nearby target muscle and will confirm muscle contraction using a hand-held nerve stimulator. The motor branch to the target muscle will be transected as close as possible to its entry point without tension. In the final step, the previous nerve stump from which the neuroma was resected will be transferred and coapted to the newly severed motor branch that innervates the target muscle and secured by 2-3 non-resorbable monofilament sutures. The surgery time is approximately 2-3 hours and it takes place in the hospital. |
| Regenerative Peripheral Nerve Interface (RPNI) | Active comparator | Procedure: Regenerative Peripheral Nerve Interface (RPNI)The RPNI procedure involves construction of a residual peripheral nerve split into several nerve fascicles and implanted into free skeletal muscle grafts. First, the surgeon identifies the nerve with a painful neuroma and resect the neuroma up to healthy fascicles. Then, a longitudinal intraneural dissection will be performed exposing its fascicles. Next, autologous muscle grafts will be harvested from a healthy donor site, and the dissected nerve stumps will be placed parallel to the muscle fibers. The nerve stump will be secured to the muscle graft, thereafter the graft will be wrapped around the nerve stump and anchored in the folded graft, thus creating an RPNI. This will be repeated for each fascicle obtained from splitting the transected nerve. Lastly, the RPNIs will be placed in a protected area. The surgery time is approximately 2-3 hours and it takes place in the hospital. |
| Standard neuroma treatment, neuroma excision, and muscle burying | Active comparator | Procedure: Standard neuroma treatment, neuroma excision, and muscle buryingThe standard neuroma treatment, also called neuroma transposition, includes excision of the terminal neuroma and burying the nerve into an adjacent deep muscle.The standard neuroma treatment entails the excision of the terminal neuroma and then implanting the nerve into an adjacent muscle. Firstly, the surgeon will identify the nerve with a painful neuroma and thereafter resect the neuroma up to healthy fascicles. Next, the surgeon will identify a nearby muscle which is not involved in joint motion and has limited output opportunities for the nerve. The nerve will then be channeled at least 1 cm inside the muscle without applying any tension to it and secured by 1-2 non-resorbable monofilament sutures. The identified nerve with the painful neuroma will not be treated with any additional therapy than the resection (e.g., diathermy, pharmacotherapy, crushing, etc.). The surgery time is approximately 1-2 hours and it takes place in the hospital. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- The participant must have a major limb amputation.
- The participant is ≥ 18 years old at the time of consent.
- The participant must be in generally good health to undergo a surgical intervention, as per the clinical investigator's opinion.
- Time since the last amputation must be over a year at the time of consent.
- The participant must have an average residual limb pain score equal or greater than 4 on the Numerical Rating Scale (NRS, 0-10) after the baseline period.
Key exclusion criteria (5 listed)
- Neurological or other conditions that affect nerve regeneration for the nerve to be treated.
- Active infection in the residual limb.
- Prior RPNI or TMR surgery of the nerve to be treated (with painful neuroma) to address postamputation pain.
- Mental disorders (e.g., schizophrenia, paranoia, psychosis, etc.), reluctance, or language difficulties that result in difficulty understanding the meaning of study participation.
- Ongoing participation in a clinical study that the clinical investigator deems detrimental to participation in this study.
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 Reinnervation (TMR)Surgical procedure used to rewire injured proximal nerves to motor nerves directly innervating an otherwise redundant target muscle. | Procedure or surgery | Targeted Muscle Reinnervation (TMR) |
| Regenerative Peripheral Nerve Interface (RPNI)Surgical procedure where the the nerve is split into fascicles and wrapped in free muscle grafts. | Procedure or surgery | Regenerative Peripheral Nerve Interface (RPNI) |
| Standard neuroma treatment, neuroma excision, and muscle buryingSurgical procedure where the neuroma is excised and the nerve stump is buried in an adjacent deep muscle. | Procedure or surgery | Standard neuroma treatment, neuroma excision, and muscle burying |
Primary outcome
Residual limb pain intensity
Time frame: Baseline to 12-month post-surgery
Difference in residual limb pain intensity will be measured by numerical rating scale (NRS, 0-10), where 0 - no pain and 10 - worst imaginable pain, between baseline period and at the 12-month follow-up visit.
2 secondary outcomes
Neuroma pain intensity
Time frame: Baseline to 12-month post-surgery
Phantom limb pain intensity
Time frame: Baseline to12-month post-surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2025.
- 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 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 28293490Woo SL, Kung TA, Brown DL, Leonard JA, Kelly BM, Cederna PS. Regenerative Peripheral Nerve Interfaces for the Treatment of Postamputation Neuroma Pain: A Pilot Study. Plast Reconstr Surg Glob Open. 2016 Dec 27;4(12):e1038. doi: 10.1097/GOX.0000000000001038. eCollection 2016 Dec.
- Background: PubMed 37131180Pettersen E, Sassu P, Reinholdt C, Dahm P, Rolfson O, Bjorkman A, Innocenti M, Pedrini FA, Breyer JM, Roche A, Hart A, Harrington L, Ladak A, Power H, Hebert J, Ortiz-Catalan M. Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial. Trials. 2023 May 2;24(1):304. doi: 10.1186/s13063-023-07286-0.
- 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.
- Background: PubMed 37063502Bjorklund KA, Alexander J, Tulchin-Francis K, Yanes NS, Singh S, Valerio I, Klingele K, Scharschmidt T. Targeted Muscle Reinnervation for Limb Amputation to Avoid Neuroma and Phantom Limb Pain in Patients Treated at a Pediatric Hospital. Plast Reconstr Surg Glob Open. 2023 Apr 13;11(4):e4944. doi: 10.1097/GOX.0000000000004944. eCollection 2023 Apr.
- 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 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.
- Derived from this study: PubMed 38557950Pettersen E, Sassu P, Pedrini FA, Granberg H, Reinholdt C, Breyer JM, Roche A, Hart A, Ladak A, Power HA, Leung M, Lo M, Valerio I, Eberlin KR, Ko J, Dumanian GA, Kung TA, Cederna P, Ortiz-Catalan M. Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain. J Vis Exp. 2024 Mar 15;(205). doi: 10.3791/66378.
- Derived from this study: PubMed 38526122Pettersen E, Sassu P, Pedrini FA, Granberg H, Reinholdt C, Breyer JM, Roche A, Hart A, Ladak A, Power HA, Leung M, Lo M, Valerio I, Eberlin KR, Kung TA, Cederna P, Souza JM, Aszmann O, Ko J, Dumanian GA, Ortiz-Catalan M. Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain. J Vis Exp. 2024 Mar 8;(205). doi: 10.3791/66379.
- 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.
Max Ortiz Catalan, PhD principal investigator
Prometei Pain Rehabilitation Center
9 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Targeted Muscle Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI) and Standard neuroma treatment, neuroma excision, and muscle burying in people with Residual Limb Pain and Amputation Neuroma, run by Prometei Pain Rehabilitation Center at 9 sites in 7 countries.
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 9 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 9 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Australia, Canada, Chile, Italy and 2 more countries. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Max Ortiz Catalan, PhD (+46708461065, maxortizc@outlook.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Residual limb pain intensity (time frame: Baseline to 12-month post-surgery). 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 NCT05009394, which also lists 10 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 9 Jan 2025.