Surgical Treatments for Postamputation Pain

Recruiting at 9 trial locations

Overseen By Max Ortiz Catalan, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Center for Bionics and Pain Research

Disqualifiers: Neurological conditions, Active infection, Mental disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks the best surgical treatment to reduce pain after limb loss. It compares three techniques: Targeted Muscle Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), and standard neuroma treatment, which removes a nerve bundle causing pain. The trial focuses on treating various pain types, including residual limb pain, neuroma pain, and phantom limb pain. Individuals who underwent major limb amputation over a year ago and still experience significant pain despite stable medication or treatments might be suitable candidates. As an unphased trial, this study offers the chance to explore innovative surgical options that could greatly enhance quality of life.

Will I have to stop taking my current medications?

The trial requires that if you are taking pain medications, your dosage must not change for at least one month before the screening visit. This means you can continue your current medications as long as the dosage remains steady.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI) are promising and safe options for treating pain after amputation.

TMR, used for over ten years, is known for reducing phantom and residual limb pain. Reviews highlight TMR's success in pain relief and rehabilitation, with no major safety issues reported.

RPNI also has a strong safety record. Studies indicate that patients experienced a 71% reduction in neuroma pain and a 53% reduction in phantom pain. Most patients expressed satisfaction with the procedure, suggesting it is well-tolerated.

The standard treatment for neuromas, which involves removing the neuroma and covering it with muscle, effectively relieves pain in 82-83% of cases. This demonstrates its reliability and safety for many patients.

Overall, these surgical techniques offer pain relief with good safety records. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard neuroma treatment, which involves simply excising the painful neuroma and burying the nerve into a muscle, both Regenerative Peripheral Nerve Interface (RPNI) and Targeted Muscle Reinnervation (TMR) offer advanced techniques to address postamputation pain. RPNI is unique because it involves splitting the nerve into fascicles and wrapping them in muscle grafts, potentially providing a more natural nerve-muscle connection and reducing pain signals more effectively. TMR, on the other hand, reroutes the nerve to a functioning muscle, which can help diminish neuroma formation and improve prosthetic control. Researchers are excited because these innovative approaches could offer more effective and long-lasting relief from postamputation pain compared to the current standard treatment.

What evidence suggests that this trial's surgical treatments could be effective for postamputation pain?

This trial studies Targeted Muscle Reinnervation (TMR) as one of the surgical treatments. Research has shown that TMR can reduce pain from neuromas and phantom limb pain (PLP) after amputation, with patients reporting less pain and improved well-being. Another treatment option in this trial is the Regenerative Peripheral Nerve Interface (RPNI), which also shows promise, with many patients experiencing pain relief and a lower risk of painful neuroma formation. One study found that 85% of patients who underwent RPNI surgery were either pain-free or had improved outcomes. The trial also includes a standard treatment for neuromas, which involves removing the painful nerve and placing it in muscle, effectively relieving pain for many patients. Each of these treatments offers hope for those dealing with pain after amputation. ^{2 6 7 8 9}

Who Is on the Research Team?

Max Ortiz Catalan, PhD

Principal Investigator

Prometei Pain Rehabilitation Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had a major limb amputation at least a year ago and are experiencing significant residual or phantom limb pain. They should be in good health for surgery, not have had prior TMR or RPNI surgeries on the affected nerve, and must not be dealing with infections or certain mental disorders that could impact their participation.

Inclusion Criteria

I have had a major limb amputation.

I have been using a stable prosthetic fitting for at least a month.

Participant must be in generally good health to undergo a surgical intervention, as per the clinical investigator's opinion

Exclusion Criteria

I have a condition that affects nerve healing in the area needing treatment.

I have an infection in the part of my limb that remains after amputation.

I had surgery on a nerve for a painful growth after an amputation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Treatment

Participants undergo one of three surgical treatments: Targeted Muscle Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), or standard neuroma treatment

1 day (surgery)

1 visit (in-person)

Short-term Follow-up

Participants are monitored for pain intensity and recovery at 1, 3, 6, and 12 months post-surgery

12 months

4 visits (in-person)

Long-term Follow-up

Participants are monitored for pain intensity and recovery at 2 and 4 years post-surgery

4 years

2 visits (in-person)

Open-label Extension (optional)

Participants may request alternative treatments if unsatisfied with initial outcomes, followed by medical evaluation and further treatment options

What Are the Treatments Tested in This Trial?

Interventions

• Regenerative Peripheral Nerve Interface (RPNI)
• Standard Neuroma Treatment, Neuroma Excision and Muscle Burying
• Standard Neuroma Treatment, Neuroma Transposition
• Targeted Muscle Reinnervation (TMR)

Trial Overview The study compares three surgical techniques to relieve postamputation pain: Targeted Muscle Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), and standard neuroma treatment involving excision and muscle burying. It's a double-blind RCT where patients will be monitored for four years.

How Is the Trial Designed?

Group I: Targeted Muscle Reinnervation (TMR) Active Control 1 Intervention

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.

Group II: Regenerative Peripheral Nerve Interface (RPNI) Active Control 1 Intervention

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.

Group III: Standard neuroma treatment, neuroma excision, and muscle burying Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Center for Bionics and Pain Research

Lead Sponsor

Trials

1

Recruited

110+

Prometei Pain Rehabilitation Center

Lead Sponsor

Trials

1

Recruited

110+

Vastra Gotaland Region

Collaborator

Trials

689

Recruited

1,455,000+

Hospital del Trabajador de Santiago

Collaborator

Trials

3

Recruited

820+

NHS Lothian

Collaborator

Trials

220

Recruited

1,334,000+

NHS Greater Clyde and Glasgow

Collaborator

Trials

10

Recruited

1,200+

NHS Grampian

Collaborator

Trials

74

Recruited

26,000+

Northwestern Memorial Hospital

Collaborator

Trials

42

Recruited

15,800+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI) are innovative surgical techniques that help address pain from nerve injuries and amputations by providing new pathways for nerve growth, which can reduce pain and improve prosthetic function.

The combination of TMR with a vascularized RPNI (vRPNI) may enhance nerve regeneration and muscle reinnervation, potentially leading to better outcomes in pain management and functional recovery for amputees.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Muscle Reinnervation Combined with a Vascularized Pedicled Regenerative Peripheral Nerve Interface. Valerio, I., Schulz, SA., West, J., et al.[2020]

Combining targeted muscle reinnervation (TMR) with regenerative peripheral nerve interface (RPNI) techniques (TMRpni) in a patient with a left above-the-knee amputation resulted in reduced phantom and nerve pain.

This innovative approach may enhance the quality of life for amputee patients as the technique gains wider acceptance and understanding in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined TMR and RPNI in a vasculopathy patient: A case report. Galbraith, LG., Najafali, D., Gatherwright, JR.[2023]

Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) are effective techniques for amputee patients, helping to reduce chronic neuropathic pain and improve prosthetic function.

The new technique 'TMRpni' combines elements of both TMR and RPNI, using nerve transfers and muscle grafts to potentially enhance outcomes for patients with residual limb pain and neuromas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TMRpni: Combining Two Peripheral Nerve Management Techniques. Kurlander, DE., Wee, C., Chepla, KJ., et al.[2020]

In a study of 63 oncologic patients who underwent amputation followed by targeted muscle reinnervation (TMR) or regenerative peripheral nerve interface (RPNI), significant reductions in both residual limb pain (RLP) and phantom limb pain (PLP) were observed, with average pain scores dropping to 1.3 and 1.9 respectively after a mean follow-up of 11.3 months.

The use of opioids decreased dramatically from 85.7% of patients preoperatively to 37.7% postoperatively, indicating that TMR and RPNI not only improve pain outcomes but also reduce reliance on pain medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces for Chronic Pain Control in the Oncologic Amputee Population. Roubaud, MS., Hassan, AM., Shin, A., et al.[2023]

Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) procedures significantly reduce pain scores in patients with symptomatic neuromas after amputation, with a mean pain score decrease from 4.3 to 1.7 points, and 92% of patients reporting resolution of nerve-related symptoms.

The study identified specific nerves, such as the sciatic nerve above the knee and the tibial nerve below the knee, that frequently require intervention for pain after amputation, suggesting that addressing these nerves during primary amputation can prevent future pain issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice Patterns and Pain Outcomes for Targeted Muscle Reinnervation: An Informed Approach to Targeted Muscle Reinnervation Use in the Acute Amputation Setting. Hoyt, BW., Gibson, JA., Potter, BK., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10942837/

Regenerative Peripheral Nerve Interface Surgery for the ... Clinical studies in human patients have also demonstrated improved pain outcomes following RPNI surgery ( Fig. 2 ). In single-cohort retrospective studies, ...

2. journals.lww.com journals.lww.com/plasreconsurg/abstract/9900/regenerative_peripheral_nerve_interface__rpni__for.2706.aspx

Regenerative Peripheral Nerve Interface (RPNI) for the... Regenerative Peripheral Nerve Interface (RPNI) has shown promise in attenuating neuropathic pain following traumatic major limb amputations. This study ...

3. neurology.org neurology.org/doi/abs/10.1212/WNL.0000000000211842

Systematic Review and Meta-analysis of Targeted Muscle ... Both TMR and RPNI are effective in alleviating post-amputation pain, with RPNI showing potential as a preventive strategy for neuroma formation.

4. josr-online.biomedcentral.com josr-online.biomedcentral.com/articles/10.1186/s13018-023-04116-6

Regenerative peripheral nerve interface reduces the ... Conclusion. This study suggested that RPNI can effectively prevent the formation of symptomatic neuroma after amputation using ultrasound.

5. frontiersin.org frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.938930/full

Regenerative Peripheral Nerve Interfaces Effectively ... performed 30 RPNI implantation procedures in 14 patients, and 85% of the patients were pain-free or reported improved outcomes upon long-term ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5222635/

Regenerative Peripheral Nerve Interfaces for the Treatment of ... Patients reported a 71% reduction in neuroma pain and a 53% reduction in phantom pain. Most patients felt satisfied or highly satisfied with RPNI surgery (75%), ...

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000211060

A Systematic Review and Meta-analysis (P5-7.001) Conclusions: This meta-analysis demonstrates that TMR and RPNI significantly reduce PLP and RLP compared to standard treatment, enhancing pain ...

8. jprasurg.com jprasurg.com/article/S1748-6815(25)00531-5/pdf

Journal Pre-proof Regenerative Peripheral Nerve Interface (RPNI) surgery is a promising new approach for managing post-amputation pain and enhancing prosthetic ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0890509621007111

“Decreasing Postamputation Pain with the Regenerative ... The RPNI demonstrates exciting potential to decrease the incidence of postamputation residual limb pain and phantom limb pain following limb loss.