Nerve Interfaces for Above-Knee Prosthetics

Overseen By Jennifer B Hamill, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Disqualifiers: Severe pain syndrome, Untreated mental health, Tobacco use, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

3 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to improve the function and user experience of above-knee prosthetics by exploring a new approach called the Regenerative Peripheral Nerve Interface (RPNI). RPNI connects nerves in the residual limb to muscle tissue, potentially allowing better control and sensation in robotic prosthetic legs. This study targets individuals with a single above-knee amputation who have had the amputation for at least six months and possess good soft tissue health in their remaining limb. Participants will undergo surgery for RPNI and have electrodes implanted, with follow-up visits to track progress over the next 3 to 12 months. The ultimate goal is to determine if this approach can help users move more naturally and with less effort. As an unphased trial, the study offers participants the opportunity to contribute to groundbreaking research that could enhance prosthetic technology for future users.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have an autoimmune condition, it must be well controlled by medication to participate.

What prior data suggests that this nerve interface is safe for above-knee prosthetics?

Research has shown that Regenerative Peripheral Nerve Interface (RPNI) surgery is generally safe and well-tolerated. Studies have found this technique to be simple and reliable, making it suitable for various surgical needs. This surgery is particularly beneficial for individuals using prosthetic devices, as it connects nerves to small muscle grafts.

In a study with diabetic amputees, those who underwent RPNI surgery reported a noticeable decrease in pain, suggesting that the procedure may have manageable risks. Another study found that RPNIs effectively manage pain from painful nerve growths (neuromas) and improve comfort for amputees.

Overall, while any surgery can have risks, the evidence so far suggests RPNI is a promising and safe option for individuals with above-knee amputations. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Regenerative Peripheral Nerve Interfaces (RPNIs) because they offer a novel way to improve control over above-knee prosthetics. Unlike traditional prosthetic solutions, which often rely on surface electrodes or mechanical attachments, RPNIs involve creating a biological interface directly on the residual nerves in the thigh. This technique allows for more precise control and feedback by directly integrating electrodes with the nerve tissue. By potentially providing more natural and intuitive movement, RPNIs could significantly enhance the quality of life for amputees.

What evidence suggests that the Regenerative Peripheral Nerve Interface is effective for above-knee prosthetics?

Research shows that a type of surgery called Regenerative Peripheral Nerve Interface (RPNI) benefits people using advanced prosthetics. In this trial, participants will undergo RPNI surgery, which studies have found can reduce pain for amputees, especially those with painful nerve growths called neuromas. For instance, people with diabetes who had amputations and underwent RPNI surgery reported much less pain. The RPNI method connects nerves to unused muscle, which can help restore some feeling and control. This connection makes the prosthetic leg move more naturally, possibly making walking easier and less tiring. Overall, RPNI surgery might offer better control and comfort for people with above-knee amputations. ^{1 2 4 6 7}

Who Is on the Research Team?

Deanna Gates, PhD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for individuals with an above-knee amputation on one leg, who have had it for at least 6 months. They should be able to walk using a motorized prosthetic leg without extra support and have healthy enough tissue in the remaining limb for surgery. People with severe scarring or those considered high-risk for surgery can't participate.

Inclusion Criteria

I can use a motorized prosthetic leg without needing shoe lifts.

I am considered low risk for surgery complications.

My mobility with a prosthesis scores 27 or higher.

Exclusion Criteria

I have a major injury on the limb opposite to the one being considered for the trial.

I suffer from severe pain, including complex regional pain syndrome or phantom pain.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Electrode Implantation

Participants undergo RPNI surgery and electrode implantation in the residual limb

1 week

1 visit (in-person)

Postoperative Follow-up and Data Collection

Regular follow-up visits to assess RPNI health, signal strength, and prosthesis use

12 months

Regular visits at 3, 6, 9, and 12 months

Electrode Explantation and Final Assessment

Participants undergo electrode explantation and complete a postoperative visit to assess recovery, pain, and adverse events

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Regenerative Peripheral Nerve Interfaces

Trial Overview The study tests a new way to control advanced robotic legs using Regenerative Peripheral Nerve Interfaces (RPNIs). It involves nerve-implanted muscle grafts that could potentially provide better movement control and sensory feedback of prosthetic limbs over time.

How Is the Trial Designed?

Group I: Regenerative Peripheral Nerve Interface (RPNI) Experimental Treatment 1 Intervention

Participants will have regenerative peripheral nerve interfaces (RPNIs) created on nerves in their residual thighs. During either the same surgery or a separate surgery, electrodes will be implanted into these RPNIs.

Regenerative Peripheral Nerve Interfaces is already approved in United States for the following indications:

Approved in United States as RPNI for:

• Neuroma pain relief
• Phantom limb pain prevention
• Prosthetic control enhancement

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a study using rat models, smaller regenerative peripheral nerve interfaces (RPNIs) constructed with 150 and 300 mg muscle grafts showed significantly better electrical signaling and muscle force compared to larger grafts of 600 and 1200 mg.

Larger RPNIs exhibited areas without regenerated muscle fibers, indicating that smaller grafts are more effective for maintaining tissue viability and enhancing neuroprosthetic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regenerative peripheral nerve interface free muscle graft mass and function. Hu, Y., Ursu, DC., Sohasky, RA., et al.[2021]

Regenerative peripheral nerve interfaces (RPNIs) successfully recorded myoelectric signals during walking in rats, demonstrating their potential for controlling prosthetic devices with over 80% reliability in predicting ankle motion.

The study showed minimal signal contamination from adjacent muscles, indicating that RPNIs can effectively encode neural activation patterns related to gait, which is crucial for their use in prosthetic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo characterization of regenerative peripheral nerve interface function. Ursu, DC., Urbanchek, MG., Nedic, A., et al.[2017]

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]

In a study involving 16 amputees who received regenerative peripheral nerve interfaces (RPNIs) for symptomatic neuromas, patients reported a significant 71% reduction in neuroma pain and a 53% reduction in phantom pain after surgery.

The RPNI procedure demonstrated a favorable safety profile, with 75% of patients expressing satisfaction with the treatment and a high likelihood of recommending it to others, indicating its efficacy as a treatment option for neuroma relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regenerative Peripheral Nerve Interfaces for the Treatment of Postamputation Neuroma Pain: A Pilot Study. Woo, SL., Kung, TA., Brown, DL., et al.[2022]

Regenerative Peripheral Nerve Interfaces (RPNIs) in a rodent model showed that adjacent RPNIs, neurotized by different nerves, can produce independent electromyographic signals during walking, indicating their potential for effective motorized prosthesis control.

The study found that the electromyographic activity from RPNIs was similar to that of control muscles, suggesting minimal crosstalk and confirming that RPNIs can encode distinct neural activation patterns associated with gait.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjacent regenerative peripheral nerve interfaces produce phase-antagonist signals during voluntary walking in rats. Ursu, D., Nedic, A., Urbanchek, M., et al.[2020]

Citations

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

Regenerative Peripheral Nerve Interface Surgery: Anatomic ... Regenerative peripheral nerve interface (RPNI) surgery has been demonstrated to be an effective tool as an interface for neuroprosthetics.

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

A Prospective Study in Major Lower Limb Amputation Patients Regenerative peripheral nerve interface (RPNI) surgery is a promising method for treating posttraumatic neuropathic pain. By suturing a ...

3. oaepublish.com oaepublish.com/articles/2347-9264.2023.101

Regenerative peripheral nerve interfaces (RPNIs) RPNIs are also an effective surgical intervention in both the prevention and treatment of postamputation pain resulting from symptomatic neuroma ...

4. withpower.com withpower.com/trial/nerve-interfaces-for-above-knee-prosthetics-eca1a

Nerve Interfaces for Above-Knee Prosthetics In a study of 28 diabetic amputees, those who underwent regenerative peripheral nerve interface (RPNI) surgery experienced a significant reduction in pain, with ...

5. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/targeted-peripheral-nerve-interface-for-post-amputation-pain-prevention

Targeted Peripheral Nerve Interface for Post-Amputation Pain ... Regenerative peripheral nerve interface (RPNI) is a novel approach to minimize the development of painful neuromas after limb amputations.

6. journals.lww.com journals.lww.com/prsgo/fulltext/2016/12000/regenerative_peripheral_nerve_interfaces_for_the.6.aspx

Regenerative Peripheral Nerve Interfaces for the Treatment ... RPNI implantation carries a reasonable complication profile while offering a simple, effective treatment for symptomatic neuromas.

7. jprasurg.com jprasurg.com/article/S1748-6815(25)00531-5/pdf

Journal Pre-proof Regenerative Peripheral Nerve Interface (RPNI) surgery is a promising new approach for managing post-amputation pain and enhancing prosthetic ...