Surgical Treatments for Neuroma Pain

(STOCAP Trial)

Recruiting at 1 trial location

Overseen By Sami Tuffaha, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Disqualifiers: Under 18, Other study participant, Others

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

Compensation: Varies

Number of Visits: 7

90 Participants Needed

Trial Summary

What is the purpose of this trial?

Amputees often suffer from relentless pain and disability resulting from symptomatic neuromas within the amputation stumps. When conservative measures fail to address these symptoms, two contemporary surgical approaches to treat symptomatic neuromas have become the most popular. Targeted muscle reinnervation (TMR) is a procedure which involves transferring the injured proximal nerve stump into a terminal nerve branch entering muscle, such that the axons from the proximal nerve stump will regenerate into the muscle and thereby prevent neuroma recurrence. Regenerative peripheral nerve interfaces (RPNIs) are muscle grafts placed on the proximal nerve stumps that serve as targets for the regenerating axons from the proximal nerve stumps. While TMR and RPNIs have demonstrated promise for the treatment of symptomatic neuromas, prospective comparative data comparing outcomes with these two approaches is lacking. The investigators have recently developed a novel approach to treat symptomatic neuromas that provides vascularized, denervated muscle targets (VDMTs) for the axons regenerating from the severed proximal nerve stump to reinnervate. This is accomplished by islandizing a segment of muscle on its blood supply and ensuring complete denervation prior to implanting the neighboring transected nerve stump into this muscle. VDMTs offer theoretical benefits in comparison to RPNIs and TMR that the investigators also aim to test in the proposed study. The investigators' objective is to enroll amputees with symptomatic neuromas into a prospective study in which amputees will be randomized to undergo TMR, RPNI, or VDMT and subsequently monitored for pain and disability for 1-year post-operatively. The investigators' specific aims are as follows: 1) Test the hypothesis that VDMTs are more effective than TMR and RPNIs with regards to treating pain and disability associated with symptomatic neuromas; 2) Provide the first level one, prospective data directly comparing the efficacy of TMR and RPNIs.

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 RPNI, TMR, VDMT for neuroma pain?

The research on vascularized denervated muscle targets (VDMTs) shows promise in treating chronic nerve pain and preventing neuroma formation, as seen in two patients with occipital neuralgia who remained pain-free for three years after treatment. ^{1 2 3 4 5}

Is surgical treatment for neuroma pain safe for humans?

Early clinical studies suggest that surgeries like RPNI and TMR, which are used to treat neuroma pain, have shown promising results and are considered safe. These procedures have been demonstrated to improve outcomes for patients with neuroma pain, indicating a good safety profile. ^{6 7 8 9 10}

How does the treatment RPNI, TMR, VDMT differ from other treatments for neuroma pain?

RPNI (Regenerative Peripheral Nerve Interface) and TMR (Targeted Muscle Reinnervation) are unique surgical treatments for neuroma pain because they provide severed nerve endings with a new target, which helps prevent painful neuroma formation. Unlike traditional methods, these techniques encourage organized nerve regeneration and have shown promising results in reducing pain and improving outcomes for amputees. ^{6 7 10 11 12}

Research Team

Sami Tuffaha, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults over 18 with chronic pain after limb amputation, who haven't had previous surgery for pain relief. They must be able to consent and participate in all tests. Women of childbearing age need a negative pregnancy test.

Inclusion Criteria

I am older than 18 years.

I have had limb pain for over 6 months after amputation without any pain surgery.

I am a woman who can have children and my pregnancy test is negative.

Exclusion Criteria

I am unable to give my consent for treatment.

I am under 18 years old.

Patient participating in another investigational device, surgical technique, or pharmacological study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Treatment

Participants undergo one of the surgical treatments: TMR, RPNI, or VDMT

1 day (surgery)

1 visit (in-person)

Post-operative Follow-up

Participants are monitored for pain and disability for 1 year post-operatively

52 weeks

6-7 visits (in-person)

Treatment Details

Interventions

• RPNI
• TMR
• VDMT

Trial Overview The study compares three surgical techniques for neuroma pain: TMR transfers injured nerves into muscle, RPNI uses muscle grafts on nerve stumps, and VDMT provides denervated muscle targets for regenerating nerves.

Participant Groups

Group I: Regenerative peripheral nerve interface (RPNI) Active Control 1 Intervention

In this operation, the surgeon will make a skin incision and carefully identify nerves that were likely to have been injured during the amputation surgery. The nerves are then "cleaned up" to enhance the possibility of healthy healing. Then the surgeon takes a small sample from a muscle (usually one close by to the nerves that are being operated on but sometimes through a second incision in the arm or leg, depending on the exact medical situation) and form something called a "muscle graft". The muscle graft is used to wrap the cleaned ends of the nerves mentioned above. This is thought to be helpful in directing the nerve healing process and reducing the risk of developing pain in the future. This operation takes 1 - 3 hours and occurs in the hospital. Follow up requires six to seven clinic visits with the surgeon over the course of one year, at which time standard questionnaires will be used to assess pain.

Group II: Vascularized, denervated muscle target (VDMT ) Active Control 1 Intervention

In this operation, the surgeon will make a skin incision and carefully identify nerves that were likely to have been injured during the amputation surgery. The nerves are then "cleaned up" to enhance the possibility of healthy healing. The surgeon will then identify a local muscle along with a small artery and vein that supply blood to part of the muscle. A small sample of muscle, still attached to the artery and vein, is then created. The nearby nerves are then nestled into this segment of muscle that is still connected to the artery and vein. This is thought to be helpful in directing the nerve healing process and reducing the risk of developing pain in the future. This operation takes 2 - 4 hours and occurs in the hospital. Follow up requires six to seven clinic visits with the surgeon over the course of one year, at which time standard questionnaires will be used to assess pain.

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

In this operation, the surgeon will make a skin incision and carefully identify nerves that were likely to have been injured during the amputation surgery. These nerves are then "cleaned up" to be rerouted and connected to smaller nerves that control individual muscles. The connection to nerves that run into muscles is thought to be helpful in directing the nerve healing process and reducing the risk of developing pain in the future. This operation takes 2 - 4 hours and occurs in the hospital. Follow up requires six to seven clinic visits with the surgeon over the course of one year, at which time standard questionnaires will be used to assess pain.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

The Plastic Surgery Foundation

Collaborator

Trials

11

Recruited

1,300+

Findings from Research

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]

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]

References

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

Vascularized Denervated Muscle Targets for Headache Surgery-Presentation and Surgical Management. [2023]

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

A comparision of percutaneous radiofrequency trigeminal neurolysis and microvascular decompression of the trigeminal nerve for the treatment of tic douloureux. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Factors That May Affect Delayed Relief Of Trigeminal Neuralgia After Microneurosurgery And The Long-Term Outcomes Associated With Delayed Relief. [2022]

4. Austria pubmed.ncbi.nlm.nih.gov

Comparison of first-time microvascular decompression with percutaneous surgery for trigeminal neuralgia: long-term outcomes and prognostic factors. [2021]

5. China pubmed.ncbi.nlm.nih.gov

Surgical treatment of trigeminal neurinomas. [2006]

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

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

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

Regenerative Peripheral Nerve Interfaces for the Treatment and Prevention of Neuromas and Neuroma Pain. [2022]

8. 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]

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

Regenerative Peripheral Nerve Interface Surgery: Anatomic and Technical Guide. [2023]

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

Targeted Muscle Reinnervation for Treatment of Neuropathic Pain. [2022]

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

Targeted Muscle Reinnervation to Improve Pain, Prosthetic Tolerance, and Bioprosthetic Outcomes in the Amputee. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

A consecutive series of targeted muscle reinnervation (TMR) cases for relief of neuroma and phantom limb pain: UK perspective. [2022]