Modified Amputation Procedure for Lower Limb Amputations

No longer recruiting at 3 trial locations

Overseen By Paul Cederna, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Must not be taking: Chronic steroids

Disqualifiers: Severe illness, Peripheral neuropathies, Smoking, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for leg amputations, called the modified amputation procedure with TMR (Targeted Muscle Reinnervation) and/or RPNI (Regenerative Peripheral Nerve Interface) construction, to enhance the use of advanced prosthetics. The goal is to improve movement, sensation, and overall function in the remaining limb after surgery. It targets individuals needing a leg amputation due to injury, limb deformities, or worsening arthritis and who are healthy enough for surgery. Participants will help researchers determine if these new techniques provide better outcomes than traditional methods. As an unphased trial, this study offers participants the chance to contribute to pioneering research that could enhance future prosthetic use and improve 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. However, if you are on chronic steroid therapy, you may be excluded from the trial.

What prior data suggests that this modified amputation procedure is safe?

Research has shown that treatments like Targeted Muscle Reinnervation (TMR) can help reduce pain after limb loss. A recent study found that TMR reduces pain more effectively than traditional methods, which is crucial because pain often becomes a major issue after an amputation.

Another study discovered that TMR helps prevent chronic phantom limb pain (pain felt in a limb that is no longer there) and residual limb pain (pain in the remaining part of the limb). This indicates that TMR is not only safe but also enhances quality of life.

The modified amputation procedure aims to improve function and reduce energy use compared to more extensive amputations. Although the data does not specifically focus on safety, these improvements suggest the procedure is well-tolerated.

Overall, these findings indicate that both the modified amputation and TMR are safe and may help relieve pain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the modified amputation procedure because it incorporates TMR (Targeted Muscle Reinnervation) and/or RPNI (Regenerative Peripheral Nerve Interface) construction, which are not standard in typical amputation surgeries. These techniques aim to improve nerve integration and reduce post-amputation pain by creating better connections between nerves and muscles. This approach promises enhanced control of prosthetics and a potential reduction in phantom limb pain, setting it apart from traditional amputation procedures that often don't address these issues.

What evidence suggests that this modified amputation procedure is effective for lower limb amputations?

Research has shown that using Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interfaces (RPNI) during amputations can greatly reduce post-surgery pain. Studies indicate that these techniques improved pain from painful nerve growths, called neuromas, in 75%-100% of patients and reduced phantom limb pain in 45%-80% of patients, with pain levels dropping by 2.4-6.2 points.

In this trial, participants in the intervention group will undergo a modified amputation procedure incorporating these techniques. This updated method aims to enhance the surgery process, leading to better movement and less energy needed when walking with a prosthetic. Early results suggest these techniques might improve muscle control and sensation in the remaining limb, making it easier to use advanced prosthetics. Overall, these methods show promise in making life after amputation more comfortable and functional. ^{1 2 6 7 8}

Who Is on the Research Team?

Matthew J Carty, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-65 who need an elective lower limb amputation due to injury, deformity, or arthritis. They must be able to communicate well, be in good health for surgery under general anesthesia, have a natural ability to heal wounds, and be motivated to follow post-op instructions.

Inclusion Criteria

I am healthy enough for surgery and general anesthesia.

I am a candidate for leg amputation due to injury, birth defects, or severe arthritis.

My body can heal wounds normally.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Procedure

Participants undergo a modified amputation procedure incorporating innervated muscle segments for enhanced prosthetic control

1 week

1 visit (in-person)

Acute Postoperative Rehabilitation

Development and implementation of a modified acute postoperative rehabilitation strategy suited to the new surgical approach

4-8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for motor unit excursion, proprioception recovery, and other postoperative outcomes

48 months

Regular follow-up visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Amputation procedure with TMR and/or RPNI construction
• Modified amputation procedure

Trial Overview The study tests a new way of performing lower limb amputations that could work better with advanced prosthetics. It aims to standardize this novel procedure for below knee (BKA) and above knee (AKA) amputations and improve motor control and sensory feedback in the residual limbs.

How Is the Trial Designed?

Group I: Intervention group Experimental Treatment 1 Intervention

Modified amputation procedure

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Massachusetts Institute of Technology

Collaborator

Trials

104

Recruited

12,810,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

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 28 diabetic amputees, those who underwent regenerative peripheral nerve interface (RPNI) surgery experienced a significant reduction in pain, with all patients in the RPNI group reporting no pain compared to 78.6% of the control group experiencing severe pain.

RPNI not only effectively managed post-amputation pain and reduced the risk of neuroma formation, but it also allowed patients to use prosthetics significantly more, without increasing operative time or complications, suggesting it is a safe and beneficial surgical technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic Regenerative Peripheral Nerve Interfaces in Elective Lower Limb Amputations. Pejkova, S., Nikolovska, B., Srbov, B., et al.[2022]

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 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]

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]

Minor amputations aim to preserve as much of the foot and leg as possible to maintain a load-bearing extremity, which is crucial for mobility and function.

Longitudinal partial amputations of the forefoot and midfoot are particularly beneficial as they help maintain stability and balance while minimizing complications associated with reduced surface area and muscle imbalance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Minor amputations: a maxi task : Part 2: From transmetatarsal amputation to hindfoot amputation]. Matamoros, R., Riepe, G., Drees, P.[2022]

Citations

1. medrxiv.org medrxiv.org/content/10.1101/2024.12.23.24319539v2.full-text

Targeted Muscle Reinnervation (TMR) or Regenerative ... The pain associated with limb amputation is known as residual limb pain (RLP) or phantom limb pain (PLP). The mechanisms and pathophysiology of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11046287/

Targeted Muscle Reinnervation and Regenerative Peripheral ... The aim of this review is to assess the effects of primary TMR/RPNI at the time of limb amputation on the incidence and intensity of post-operative neuroma and ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0020138325006254

PROCESS guided Case series of Primary Targeted Muscle ... This case series demonstrates promising outcomes for Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interfaces (RPNI) ...

4. 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.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36965013/

Targeted muscle reinnervation and regenerative peripheral ... For pain treatment, TMR and RPNI improved neuroma pain in 75%-100% of patients and phantom limb pain in 45%-80% of patients, averaging a 2.4-6.2-point reduction ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1748681524001670

Review The effectiveness of targeted muscle reinnervation ... TMR has emerged as a promising surgical technique for reducing pain and improving the quality of life for individuals traversing the journey of lower limb ...

7. checkpointsurgical.com checkpointsurgical.com/wp-content/uploads/2020/08/CS-9094-MKT-160-D_TMR_Abstracts.pdf

Targeted Muscle Reinnervation (TMR): Current Research ... In a recent randomized controlled trial, targeted muscle reinnervation was recently shown to reduce postamputation pain relative to conventional neuroma ...

8. thieme-connect.com thieme-connect.com/products/ejournals/pdf/10.1055/a-2521-2199.pdf?issue=10.1055/s-015-61630

Targeted Muscle Reinnervation—an Up-to-Date Review TMR has since been shown to be effective in the prevention and treatment of chronic postamputation phantom and residual limb pain in both upper ...