Neural Interface for Upper Limb Amputation

(PSI Trial)

Overseen By Melissa S Schmitt

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Bilateral amputation, Uncontrolled diabetes, Neuropathy, others

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

Compensation: Varies

Number of Visits: Unknown

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help individuals with an upper limb amputation feel where their missing limb would be through nerve stimulation. Participants receive a special device, the Chronically Implanted Neural and Muscular Interface, which sends tiny electrical signals to the nerves, creating sensations similar to having a real hand. Researchers hope this can improve the control and feel of prosthetic limbs. The trial suits those who have had one arm amputated, possess healthy nerves in the remaining part, and have used a prosthetic for at least a month. As an unphased trial, it offers a unique opportunity for participants to contribute to groundbreaking research that could enhance prosthetic technology for future patients.

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 study team to get a clear answer.

What prior data suggests that this neural interface is safe for upper limb amputees?

Research shows that using a Chronically Implanted Neural and Muscular Interface holds promise for safety in humans. This treatment employs Functional Electrical Stimulation (FES), which involves applying small electric currents to nerves. Studies have found that this type of nerve stimulation is usually well-tolerated and can increase comfort and reduce fatigue compared to methods like surface electromyography (sEMG).

Although specific data from this exact study is not yet available, the technology behind these neural interfaces has been studied for safety and ease of use. Users of similar systems report more frequent use of their prosthetic limbs with less discomfort. This suggests that the treatment is relatively safe and can enhance the daily lives of those with upper limb amputations. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the chronically implanted neural and muscular interface for upper limb amputation because it offers a groundbreaking approach to restoring sensation and function. Unlike standard prosthetic options, which primarily focus on mechanical movement, this treatment uses Functional Electrical Stimulation (FES) to directly interface with nerves and muscles, potentially allowing for more natural proprioceptive sensations. This novel mechanism of action could lead to a significant improvement in how amputees perceive and control their prosthetic limbs, making it a promising advancement in the field of limb restoration.

What evidence suggests that the Chronically Implanted Neural and Muscular Interface is effective for upper limb amputation?

Research shows that long-term implanted devices in nerves and muscles can enhance how upper limb amputees control prosthetic arms. In this trial, participants will receive the Chronically Implanted Neural and Muscular Interface to explore this potential. Studies have found that small electric currents, known as functional electrical stimulation, help create sensations that inform the brain about limb movement and position, similar to a natural hand. This method aims to improve the ability to "feel" and control a prosthetic arm, resulting in more natural movements. Early results suggest that this technology could significantly enhance prosthetic limb function, providing users with better control and a more intuitive experience. Previous patients successfully used these devices long-term to improve prosthetic control. ^{1 2 5 6 7}

Who Is on the Research Team?

Emily L Graczyk, PhD

Principal Investigator

Louis Stokes VA Medical Center, Cleveland, OH

Are You a Good Fit for This Trial?

This trial is for individuals with a single upper limb amputation who are medically fit for anesthesia, have been using a prosthesis fitted by a specialist for at least one month, and can follow the study protocol. They must have good nerve function in the remaining limb and be mentally competent to participate. Pregnant women or those not preventing pregnancy, non-English speakers, people unfit for surgery, with uncontrolled diabetes or severe pain that interferes with activities are excluded.

Inclusion Criteria

Willingness and availability to follow the study protocol

A psychologist has confirmed I'm mentally fit for the study.

My remaining limb has working nerves.

Exclusion Criteria

I am not healthy enough for surgery.

I am able to understand and agree to the study's requirements.

Pregnancy, or those who are of childbearing potential, unwilling to prevent pregnancy during the trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Testing

Participants are implanted with neural and muscular interfaces and undergo initial testing to characterize proprioceptive sensations using Functional Electrical Stimulation (FES).

4-8 weeks

Proprioceptive Sensation Characterization

Characterization of proprioceptive sensations elicited by peripheral nerve stimulation, including testing of time-varying Peripheral Nerve Stimulation (PNS) patterns and paired agonist-antagonist stimulation strategies.

6 months

Monthly visits for assessments

Mechanisms Investigation

Investigation of the mechanisms of stimulation-evoked proprioception, including motor block tests and Targeted Muscle Reinnervation.

6 months

Monthly visits for assessments

Integration with Motor Control

Integration of proprioceptive stimulation with motor control during posture matching tasks, including virtual reality tasks and psychometric dissimilarity rating tasks.

12 months

Monthly visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after the main intervention phases.

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Chronically Implanted Neural and Muscular Interface

Trial Overview The study aims to create sensations of hand position and movement (proprioception) in amputees by stimulating nerves through Functional Electrical Stimulation (FES). It will test different stimulation placements to evoke proprioceptive sensations and develop advanced prosthetic controllers based on these findings.

How Is the Trial Designed?

Group I: Chronically Implanted Neural and Muscular Interface Experimental Treatment 1 Intervention

6 eligible participants will be chronically implanted with neural and muscular interfaces to characterize proprioceptive sensations using Functional Electrical Stimulation (FES).

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

The novel Regenerative Peripheral Nerve Interface (RPNI) demonstrated reliable signal generation from a residual nerve after a 14-month maturation period, indicating its potential for effective control of neuroprosthetic limbs.

Electromyographic signals from the RPNI were consistent and strong, exceeding 4 mV, with no signs of muscle denervation or significant tissue damage, suggesting long-term viability and safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrically stimulated signals from a long-term Regenerative Peripheral Nerve Interface. Langhals, NB., Woo, SL., Moon, JD., et al.[2020]

The Regenerative Peripheral Nerve Interface (RPNI) provides reliable and consistent signals for upper-limb neuroprosthetic control, maintaining a high signal-to-noise ratio for up to 1054 days in participants.

One participant achieved over 94% accuracy in real-time prosthetic performance for 604 days and completed complex tasks with 99% accuracy for 611 days, demonstrating the long-term efficacy of RPNIs in controlling prosthetic devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term upper-extremity prosthetic control using regenerative peripheral nerve interfaces and implanted EMG electrodes. Vu, PP., Vaskov, AK., Lee, C., et al.[2023]

Current prosthetic treatments for upper limb amputation provide limited functionality compared to natural arms, leading to high abandonment rates despite good acceptance among motivated patients.

Recent advancements in neural interface technologies, both invasive and noninvasive, show promise for improving control and functionality of prostheses, potentially enhancing the quality of life for amputees.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural interfaces for control of upper limb prostheses: the state of the art and future possibilities. Schultz, AE., Kuiken, TA.[2011]

Targeted muscle reinnervation (TMR) successfully enhances nerve activity in amputees by redirecting nerves to remnant muscles, allowing for better control signals for prosthetic devices.

In a study involving three above-elbow amputees over 2.5 years, the use of wireless myoelectric sensors implanted at reinnervation sites led to significant functional improvements in controlling robotic arms compared to traditional surface electrode methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term implant of intramuscular sensors and nerve transfers for wireless control of robotic arms in above-elbow amputees. Salminger, S., Sturma, A., Hofer, C., et al.[2021]

The review highlights the evolution of implantable electrical interfaces with the nervous system, emphasizing the need for a systematic approach to product development that incorporates scientific understanding, technology availability, and regulatory pathways.

Despite some successes in neural prosthetics, the field faces challenges with dubious claims and the necessity for rigorous assessment to ensure safety and efficacy in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural Prosthetics:A Review of Empirical vs. Systems Engineering Strategies. Loeb, GE.[2023]

A comprehensive review of 343 studies on implantable electrodes for neural and muscular activity revealed that most research uses small animal models, particularly rats, with only 37% of studies providing chronic testing data that could inform long-term performance.

The analysis suggests that a combination of small animals for initial testing and large animals for long-term biocompatibility studies is essential for developing reliable bionic prostheses, despite the higher costs associated with large animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental Testing of Bionic Peripheral Nerve and Muscle Interfaces: Animal Model Considerations. Aman, M., Bergmeister, KD., Festin, C., et al.[2020]

The development of a percutaneous osseointegrated interface allows for permanent and reliable bidirectional communication between prosthetic limbs and the human body, enabling intuitive neural control and improving the quality of life for amputees.

In a study involving one subject over more than a year, implanted electrodes demonstrated more precise and reliable control of the prosthetic limb compared to surface electrodes, providing stable myoelectric pattern recognition and sensory feedback during daily activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An osseointegrated human-machine gateway for long-term sensory feedback and motor control of artificial limbs. Ortiz-Catalan, M., Håkansson, B., Brånemark, R.[2021]

Neuroprostheses and hybrid bionic systems are being developed to restore motor and sensory functions in disabled patients, utilizing various types of peripheral interfaces for neuromuscular stimulation and signal recording.

The review highlights the evolution of both non-invasive and invasive electrode technologies, addressing their effectiveness in interfacing with the nervous system and the challenges related to electrode design and tissue injury, which are crucial for improving the performance of artificial and robotic prostheses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems. Navarro, X., Krueger, TB., Lago, N., et al.[2006]

The agonist-antagonist myoneural interface is a new surgical technique aimed at improving control over prosthetic limbs for amputees.

This approach not only enhances voluntary movement of prostheses but also helps maintain sensory feedback and reduces muscle wasting in the affected limb.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Agonist-Antagonist Myoneural Interface. Carty, MJ., Herr, HM.[2022]

The agonist-antagonist myoneural interface (AMI) allows for improved control and feedback from prosthetic devices by preserving natural muscle dynamics, enabling bidirectional communication between the muscles and the central nervous system.

This study introduces a dual-stage surgical procedure to implement AMIs in patients with traumatic or previous amputations, showing that the AMI maintains robust physiological function and can integrate into the body's reflexive systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards functional restoration for persons with limb amputation: A dual-stage implementation of regenerative agonist-antagonist myoneural interfaces. Srinivasan, SS., Diaz, M., Carty, M., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1934148210005174

Neural Interfaces for Control of Upper Limb Prostheses Current treatment of upper limb amputation restores some degree of functional ability, but this ability falls far below the standard set by the natural arm.

2. withpower.com withpower.com/trial/phase-11-2021-352dc

Neural Interface for Upper Limb Amputation (PSI Trial) The purpose of this study is to characterize proprioceptive sensations in the missing limb of upper limb amputees using nerve stimulation, and to develop ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10126717/

Long-term upper-extremity prosthetic control using ... This study demonstrates the potential of RPNIs and implanted EMG electrodes as a long-term interface for enhanced prosthetic control.

4. mdpi.com mdpi.com/2075-1702/13/9/804

Robotic Prostheses and Neuromuscular Interfaces These medical devices are recognized for providing mobility to the amputated limb and are categorized based on their activation system. Body-powered activation ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03432325

Neural Enabled Prosthesis for Upper Limb Amputees The purpose of this study is to evaluate a new prosthetic system for transradial amputees called the neural-enabled prosthetic hand (ANS-NEPH).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12086952/

Investigating the Feasibility and Safety of Osseointegration ... User experience: ONIs increase daily prosthesis use by ~6 hours compared to sEMG, with higher comfort and reduced muscle fatigue, while sEMG is ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9996795/

Upper limb prostheses: bridging the sensory gap - PMC This review outlines the nature of the problems underlying sensory restitution, the engineering methods that attempt to address this deficit and the surgical ...