Surgical Treatments for Postamputation Pain

Recruiting in Palo Alto (17 mi)

+9 other locations

Overseen by Max Ortiz Catalan, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Center for Bionics and Pain Research

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment for postamputation pain?

Research shows that targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) can reduce pain after amputation, including phantom limb pain and neuroma pain. These techniques help nerves grow into muscles, which can decrease pain and improve the use of prosthetics. ^{1 2 3 4 5}

Is the surgical treatment for postamputation pain generally safe for humans?

Research on targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) suggests these procedures are generally safe and can reduce pain after amputation, improving quality of life. These techniques have been used in various patient populations, including those with cancer and vascular issues, with reported benefits in pain reduction and improved prosthetic function. ^{1 2 3 4 5}

How is the treatment for postamputation pain using TMR and RPNI different from other treatments?

The treatment using Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI) is unique because it provides new targets for nerves to connect with, which can help reduce pain from nerve injuries after amputation. This approach can improve the quality of life by reducing phantom and nerve pain, unlike traditional methods that may rely more on medications. ^{1 2 3 4 5}

Research Team

Max Ortiz Catalan, PhD

Principal Investigator

Prometei Pain Rehabilitation Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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+

Boubou Hallberg

Vastra Gotaland Region

Chief Executive Officer since 2024

MD from Uppsala University

Madeleine Jonsson

Vastra Gotaland Region

Chief Medical Officer since 2023

MD from Karolinska Institute

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+

Adam Coldwells

NHS Grampian

Chief Executive Officer since 2023

BSc in Health and Social Care Management

Dr. Hugh Bishop

NHS Grampian

Chief Medical Officer

MD, specialization in Pediatric Oncology

Northwestern Memorial Hospital

Collaborator

Trials

42

Recruited

15,800+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Marschall S. Runge

University of Michigan

Chief Executive Officer since 2015

MD, PhD

Karen McConnell

University of Michigan

Chief Medical Officer since 2020

MD

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

Findings from Research

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]

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]

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 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]

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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Outcomes of Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces for Chronic Pain Control in the Oncologic Amputee Population. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Combined TMR and RPNI in a vasculopathy patient: A case report. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Targeted Muscle Reinnervation Combined with a Vascularized Pedicled Regenerative Peripheral Nerve Interface. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

TMRpni: Combining Two Peripheral Nerve Management Techniques. [2020]