TMR + RPNI for Amputation-Related Pain

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Under 18, Non-oncologic amputation, others

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

Compensation: Varies

Number of Visits: 3

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two surgical methods, TMR (targeted muscle reinnervation) and RPNI (regenerative peripheral nerve interfaces), to reduce chronic pain in individuals who have undergone amputation due to cancer. These surgeries connect cut nerves to muscles, potentially managing pain in the remaining limb and alleviating phantom limb sensations. The trial will assess the effectiveness of each technique both individually and in combination. Suitable candidates include those who have had an amputation due to cancer and experience significant pain in their remaining limb or phantom limb. As an unphased trial, this study provides a unique opportunity to explore innovative surgical techniques that could greatly enhance quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these surgical techniques are safe for alleviating amputation-related pain?

Research has shown that both targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) surgeries are safe options for treating pain after an amputation. Studies have found that RPNI not only is safe but also effectively reduces pain post-amputation. It is described as simple and dependable, making it suitable for various surgeries.

TMR has also proven safe, with most patients experiencing less pain from neuromas (painful nerve growths) after the surgery. Combining TMR with RPNI is safe and leads to significant pain relief and improved outcomes for patients. These findings suggest that both surgical techniques, whether used alone or together, are well-tolerated and effective in managing pain related to amputation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of Regenerative Peripheral Nerve Interface (RPNI) and Targeted Muscle Reinnervation (TMR) for managing amputation-related pain because these techniques offer a novel approach by directly addressing nerve pain at its source. Unlike traditional pain management options like medications or nerve blocks, which primarily mask symptoms, RPNI and TMR aim to restore function and reduce pain by rerouting and reconnecting nerves to healthy muscle tissue. This could potentially lead to more enduring relief and improved limb function for amputees. By integrating these advanced surgical techniques, researchers hope to offer a more effective and sustainable solution for individuals suffering from persistent pain after amputation.

What evidence suggests that this trial's surgical techniques could be effective for alleviating amputation-related pain?

Research shows that two types of surgeries, targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), hold promise for reducing pain after amputation. In this trial, participants will receive either TMR, RPNI, or a combination of both in different treatment arms. Studies indicate that TMR can significantly reduce long-term pain in individuals who have lost a limb and improve their quality of life, with more than half of the patients experiencing lasting pain relief. RPNI surgery effectively reduces painful nerve growths and helps manage post-amputation pain. Combining TMR and RPNI may enhance pain relief further, as each targets different aspects of nerve healing. Overall, these treatments offer hope for those dealing with ongoing pain in the remaining limb or phantom pain after amputation. ^{2 4 6 7 8}

Who Is on the Research Team?

Margaret S Roubaud

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for cancer patients who have chronic pain after limb amputation. Participants should be experiencing residual or phantom limb pain. Specific eligibility criteria are not provided, but typically include factors like overall health status and time since amputation.

Inclusion Criteria

Patients able to complete informed consent

I have nerves in my amputation stump or reconstructed area that can be used for surgery.

I am 18 or older and getting an amputation due to cancer.

Exclusion Criteria

I am unable to give consent by myself.

I have not had an amputation for immediate relief with a life expectancy under 3 months.

I am under 18 years old.

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 the surgical procedures: TMR, RPNI, or TMR combined with RPNI

1 week

Follow-up

Participants are monitored for safety and effectiveness after the surgical treatment

12 months

Follow-up visits at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Regenerative Peripheral Nerve Interface Surgery
• Targeted Muscle Reinnervation

Trial Overview The study tests two surgical techniques: Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface Surgery (RPNI), both alone and combined, to see if they reduce chronic pain in the remaining limb or phantom sensation post-amputation.

How Is the Trial Designed?

Group I: Arm 3 (TMI + RPNI) Experimental Treatment 3 Interventions

Patients undergo TMR in combination with RPNI.

Group II: Arm 2 (regenerative peripheral nerve interface) Active Control 2 Interventions

Patients undergo RPNI procedure.

Group III: Arm 1 (targeted muscle reinnervation) Active Control 2 Interventions

Patients undergo TMR procedure.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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]

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]

In a study of 90 patients, those who received prophylactic regenerative peripheral nerve interfaces during limb amputation had a significantly lower incidence of symptomatic neuromas (0.0%) compared to control patients (13.3%).

Patients with the nerve interfaces also reported much less phantom limb pain (51.1%) compared to control patients (91.1%), indicating that these interfaces may help prevent pain by reducing neuroma formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain. Kubiak, CA., Kemp, SWP., Cederna, PS., et al.[2022]

Effective management of peripheral nerves during amputation surgery is crucial to reduce nerve-related pain, which is common among amputees and can lead to dissatisfaction and functional impairment.

Emerging techniques like regenerative peripheral nerve interface (RPNI) and targeted muscle reinnervation (TMR) show promise in improving outcomes related to neuroma and phantom pain, suggesting a shift from traditional methods like traction neurectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral Nerve Management in Extremity Amputations. Richards, JT., Baird, MD., Tintle, SM., et al.[2022]

Targeted muscle reinnervation (TMR) is an effective microsurgical technique that enhances the connection between nerves and muscles, improving the functionality of prosthetic devices.

Postoperative treatments, including functional electrical stimulation (FES) and nerve growth factor (NGF) injections, significantly promote nerve regeneration and improve muscle function recovery in a rat model, indicating their potential benefits in enhancing outcomes after TMR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Biological and Physical Enhancement on Targeted Muscle Reinnervation. Zhong, S., Zhang, Z., Su, H., et al.[2022]

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]

In a study involving 60 adult rats with sciatic nerve injuries, the regenerative peripheral nerve interface (RPNI) significantly increased neuronal density in the dorsal root ganglia (DRG) compared to control and nerve stump implantation groups, indicating its potential for enhancing nerve recovery.

RPNI also reduced neuronal apoptosis and increased the expression of neurotrophic factors (like NGF, NT-3, BDNF, and GDNF) in the DRGs, suggesting that it provides neuroprotective effects that could improve outcomes in delayed peripheral nerve repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of regenerative peripheral nerve interface on dorsal root ganglia neurons following peripheral axotomy. Wang, Z., Zhang, D., Yi, XZ., et al.[2022]

In a study involving 36 Fischer rats with induced neuroma pain, both targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) surgeries significantly reduced pain scores compared to control groups, indicating their effectiveness in managing neuroma pain.

Both TMR and RPNI surgeries resulted in neuromuscular junction reinnervation and decreased markers of pain and regeneration in sensory neurons, suggesting they are promising techniques for improving outcomes in patients with nerve injuries or amputations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Direct Comparison of Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces to Prevent Neuroma Pain. Senger, JB., Hardy, P., Thorkelsson, A., et al.[2023]

In a study of 142 patients who underwent upper extremity amputations, 42% experienced neuropathic pain, with traumatic and transhumeral amputations significantly increasing the risk of developing this pain.

The findings suggest that for patients at higher risk of neuropathic pain, such as those with traumatic or transhumeral amputations, proactive treatment options like targeted muscle reinnervation (TMR) or regenerative peripheral nerve interfaces (RPNIs) should be considered to mitigate pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors for Neuropathic Pain Following Major Upper Extremity Amputation. Lans, J., Hoftiezer, Y., Lozano-Calderón, SA., et al.[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]

Citations

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A Prospective Study in Major Lower Limb Amputation Patients RPNI surgery leverages the processes of reinnervation to successfully treat residual limb pain and improve psychosocial outcomes in patients with chronic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05008185

Regenerative Peripheral Nerve Interfaces to Treat Painful ... This will be a prospective observational study that seeks to provide a comprehensive assessment of the outcomes after RPNI surgery compared to standard of ...

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From concept to clinical practice-Unraveling the adoption ... Regenerative Peripheral Nerve Interface (RPNI) surgery is a promising new approach for managing postamputation pain and enhancing prosthetic control. The ...

4. mayoclinic.org mayoclinic.org/medical-professionals/orthopedic-surgery/news/rpni-lowers-post-amputation-pain/mac-20537657

RPNI lowers post-amputation pain It prophylactically reduces potentially symptomatic neuromas through autologous free muscle grafts, often from the amputated limb, implanting ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38348364/

Regenerative Peripheral Nerve Interface (RPNI) Surgery ... Expected outcomes: Articles describing RPNI surgery for postamputation pain have shown favorable outcomes, with significant reduction in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10351954/

Regenerative Peripheral Nerve Interface Surgery: Anatomic ... Regenerative peripheral nerve interface surgery is safe, straightforward, reproducible, reliable, effective, and scalable to many surgical specialties.

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“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.

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Targeted Muscle Reinnervation (TMR) or Regenerative ... Targeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI) for pain prevention in patients with limb amputation: a ...