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

Trial Summary

What is the purpose of this trial?

Individuals with an above-knee lower limb amputation are known to walk more slowly, expend more energy, have a greater risk of falling, and have reduced quality of life compared to individuals without amputation and those with below knee amputation. One of the driving factors behind these deficits is the lack of active function provided by above-knee prostheses with prosthetic knees and ankles. While many prosthetic devices have been developed for functional restoration after major lower extremity amputation, there remains no stable interface to facilitate reliable, long-term volitional control of an advanced robotic limb capable moving multiple joints. Moreover, there is no existing interface that provides useful sensory feedback that in turn enhances the functional capabilities of the prosthesis. To achieve both greater signal specificity and long-term signal stability, we have developed a biologic interface known as the Regenerative Peripheral Nerve Interface (RPNI). An RPNI consists of a peripheral nerve that is implanted into a free muscle graft that would otherwise go unused in the residual limb. As the nerve grows, it reinnervates the free muscle graft which undergoes a predictable sequence of revascularization and regeneration. The main questions it aims to answer are: 1. Can the amplitude, movement specificity and stability of sciatic nerve RPNI electromyography (EMG) signals be detected up to one year post RPNI surgery? 2. Do RPNIs contain information to enable control of a physical motorized prosthetic leg with multiple degrees of freedom? 3. Does stimulation of sciatic nerve RPNIs provides meaningful sensory feedback? Consenting participants with unilateral transfemoral amputation (TFA) will: 1. Undergo RPNI surgery and electrode implantation in the residual limb. 2. Attend regular follow-up visits following surgery to assess the health and signal strength of the RPNIs and their ability to use a prescribed prosthesis between 3- and 12-months following implantation. 3. Undergo explantation of electrodes following the conclusion of data collection.

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 data supports the effectiveness of the treatment Regenerative Peripheral Nerve Interfaces (RPNI) for above-knee prosthetics?

Research shows that RPNIs can help manage post-amputation pain and prevent neuroma (painful nerve growth) formation. In a study, patients with RPNI reported significantly less pain and used their prosthetics more effectively compared to those without RPNI. ^{1 2 3 4 5}

Is the Regenerative Peripheral Nerve Interface (RPNI) surgery safe for humans?

Studies on RPNI surgery, originally designed for prosthetic control, have shown it to be safe in humans, with no major complications reported in patients undergoing the procedure for post-amputation pain and neuroma prevention. ^{1 2 3 4 5}

How is the treatment Regenerative Peripheral Nerve Interfaces (RPNI) unique for above-knee prosthetics?

Regenerative Peripheral Nerve Interfaces (RPNIs) are unique because they use muscle grafts to connect nerves, allowing for high-fidelity control of prosthetic devices by translating nerve signals into movements. This approach not only aids in prosthetic control but also helps prevent painful neuroma formation after amputation, which is not addressed by traditional prosthetic solutions. ^{1 2 3 4 5}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

In vivo characterization of regenerative peripheral nerve interface function. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Adjacent regenerative peripheral nerve interfaces produce phase-antagonist signals during voluntary walking in rats. [2020]

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

Regenerative peripheral nerve interface free muscle graft mass and function. [2021]

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

Regenerative Peripheral Nerve Interfaces for the Treatment of Postamputation Neuroma Pain: A Pilot Study. [2022]

5. North Macedonia pubmed.ncbi.nlm.nih.gov

Prophylactic Regenerative Peripheral Nerve Interfaces in Elective Lower Limb Amputations. [2022]