Surgical Treatments for Neuroma Pain

(STOCAP Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests three surgical methods to help amputees suffering from severe pain due to nerve issues in their amputation stumps. The trial compares Targeted Muscle Reinnervation (TMR), Regenerative Peripheral Nerve Interfaces (RPNIs), and a new method using Vascularized, Denervated Muscle Targets (VDMTs) to determine which best reduces pain and disability. The researchers aim to discover if the new VDMT approach is more effective than the other two. They seek amputees who have experienced uncontrollable pain for over six months and have not undergone surgery for pain relief. Participants will be monitored for pain and disability for a year after surgery. As an unphased trial, this study offers participants the chance to explore innovative treatments that could significantly improve their 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.

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

Research shows that surgeries like RPNI, VDMT, and TMR can help reduce pain from neuromas in amputees. These surgeries aim to lessen pain by promoting better nerve healing after an amputation.

Studies have found that RPNI surgery can significantly reduce neuroma pain. In one study, patients reported a 71% decrease in neuroma pain and a 53% reduction in phantom limb pain, providing relief in areas of the body no longer present.

VDMT is a newer technique, but early research suggests it is a safe and effective method for preventing and treating neuromas. Short-term results show it can successfully reduce pain in patients who have undergone the procedure.

For TMR, evidence indicates it can almost completely eliminate pain in the affected nerves. In one study, 14 out of 15 patients no longer felt pain in the treated nerves. Another study found that TMR patients had no pain in their remaining limb, and only 7% experienced phantom limb pain.

Overall, these treatments are generally well-tolerated, with patients experiencing significant pain relief. However, discussing potential risks and benefits with a healthcare provider is important before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about surgical treatments like RPNI, VDMT, and TMR for neuroma pain because they offer a new approach to nerve healing and pain reduction after amputation. Unlike traditional treatments that might focus on medication or standard nerve repair, these methods involve using muscle grafts and redirecting nerves to promote healthier healing paths. RPNI wraps nerve ends in muscle grafts to aid recovery, VDMT uses a muscle segment connected to blood vessels to support nerve healing, and TMR connects injured nerves to smaller nerves that control muscles. These innovative techniques aim to reduce the risk of painful neuroma development by guiding nerve regeneration more effectively.

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

Research has shown that both Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interfaces (RPNIs), separate treatment options in this trial, effectively reduce pain from neuromas, which are painful nerve growths that can occur after an amputation. Studies indicate that TMR improves pain levels in about 72.5% of patients, and combined data suggests it can nearly eliminate pain in the remaining limb. RPNIs have reduced neuroma pain by 71% and help prevent new neuromas from forming. The new Vascularized Denervated Muscle Target (VDMT) method, another treatment option in this trial, is still under study. It aims to improve results by providing a healthier muscle area for nerve healing. While VDMT looks promising, more research is needed to confirm its effectiveness compared to TMR and RPNIs. ^{2 4 6 7 8}

Who Is on the Research Team?

Sami Tuffaha, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 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 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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

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

Regenerative Peripheral Nerve Interface Surgery for the ... For the treatment of neuropathic pain, improvements in pain were consistently high for both TMR and RPNI surgery: 75 to 100%. When used prophylactically to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11932616/

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 ...

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

Regenerative Peripheral Nerve Interfaces Effectively ... Several current clinical trials have confirmed the effectiveness of RPNI in the prevention of neuromas and phantom limb pain (Zimmermann, 2001; ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2667396722000799

Regenerative peripheral nerve interface for the treatment of ... Woo et al demonstrated a 71% reduction in neuroma pain, and a 53% reduction in phantom pain, in 16 amputees (3 upper extremities and 14 lower extremities), ...

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

Regenerative Peripheral Nerve Interface Surgery: Anatomic ... This theory has been supported in the literature, as the RPNI data demonstrate significant reduction in neuroma pain and phantom limb pain, and ...

7. 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 ...

8. academic.oup.com academic.oup.com/bjs/article/110/Supplement_7/znad258.483/7254119

1259 Clinical Outcomes of Vascularised Versus Free ... The currently available data support the use of both fRPNI and vRPNI for the treatment of upper extremity neuromas, both after the development of symptoms and ...