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

Trial Summary

What is the purpose of this trial?

This clinical trial evaluates two surgical techniques (targeted muscle re-innervation \[TMR\] and regenerative peripheral nerve interfaces \[RPNI\]) alone and in combination for the alleviation of chronic residual limb and phantom limb pain in cancer patients who have had an amputation. Chronic residual limb pain and phantom limb pain are debilitating outcomes of traumatic and oncologic amputation. Emerging microsurgical treatments for post-amputation pain are very promising. TMR and RPNI are both approved surgical techniques that involve connecting cut nerves to parts of the muscle as a way to heal and protect the nerves. This trial evaluates these techniques alone and in combination for the treatment of residual and phantom limb pain in cancer patients who have received an amputation.

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 data supports the effectiveness of the treatment Regenerative Peripheral Nerve Interface Surgery, Targeted Muscle Reinnervation for amputation-related pain?

Research shows that combining Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interfaces (RPNI) can reduce pain after amputation, such as phantom limb pain and neuroma pain, by providing new targets for nerve growth, which helps in nerve healing and reduces pain. ^{1 2 3 4 5}

Is TMR + RPNI safe for humans?

TMR (Targeted Muscle Reinnervation) and RPNI (Regenerative Peripheral Nerve Interface) have been used to help reduce pain after amputations, and they are generally considered safe. These techniques have been shown to improve pain outcomes and quality of life for amputee patients, with no major safety concerns reported in the studies. ^{1 2 5 6 7}

How does the TMR + RPNI treatment for amputation-related pain differ from other treatments?

The TMR + RPNI treatment is unique because it combines two advanced surgical techniques to provide new targets for nerve growth, potentially reducing pain from amputated nerves. This approach not only helps in pain reduction but also enhances nerve regeneration and muscle reinnervation, which is not typically addressed by standard treatments. ^{1 2 8 9 10}

Research Team

Margaret S Roubaud

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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 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) 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]

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 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]

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 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]

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]

References

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

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

2. 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]

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

Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain. [2022]

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

Peripheral Nerve Management in Extremity Amputations. [2022]

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Risk Factors for Neuropathic Pain Following Major Upper Extremity Amputation. [2023]

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

A Direct Comparison of Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces to Prevent Neuroma Pain. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of regenerative peripheral nerve interface on dorsal root ganglia neurons following peripheral axotomy. [2022]

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

Efficacy of Biological and Physical Enhancement on Targeted Muscle Reinnervation. [2022]