Regenerative Peripheral Nerve Interface for Control of Lower Limb Prostheses

NCT06275282 | Recruiting DMC FDA Device

• 1 other identifier: HUM00235849
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 2.Do RPNIs contain information to enable control of a physical motorized prosthetic leg with multiple degrees of freedom?
3. 3.Does stimulation of sciatic nerve RPNIs provides meaningful sensory feedback?
4. 4.Undergo RPNI surgery and electrode implantation in the residual limb.
5. 5.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.
6. 6.Undergo explantation of electrodes following the conclusion of data collection.

Conditions

Amputation; Prostheses and Implants

Keywords

RPNI; Regenerative Peripheral Nerve Interface; Implanted Electrodes

Outcome Measures

Primary Outcomes (6)

• Intensity of pain in residual and phantom limbs

  Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity-Short Form 3a

  through study completion, an average of 1 year

• Neuropathic Pain in residual limb

  Leeds Assessment of Neuropathic Symptoms and Signs (LANSS)

  through study completion, an average of 1 year

• Health-Related Quality of Life

  Participants will complete the RAND 36-Item Short Form Health Survey (SF-36)

  through study completion, an average of 1 year

• Amplitude and signal-to-noise ratio for each RPNI

  Participants will be instructed to make large, sustained movements with their phantom lower extremity while in a seated position to estimate their maximum voluntary contraction. They will repeat this process five times for each movement. The signal-to-noise ratio (SNR) will be calculated as the ratio of that signal to the quiescent period signals.

  Postoperatively at each experimental visit at 3,6,9 & 12 months

• Classification accuracy for movements of the phantom limb

  Participants will move their phantom limb to match a virtual limb shown on a screen. We will measure how accurately we can predict the intended movement using muscle activity signals from RPNIs and residual muscles

  Postoperatively at each experimental visit at 3,6,9 & 12 months

• Threshold for sensation after electrical stimulation of RPNI

  We will stimulate RPNIs electrically through the implanted electrodes. We will quantify the charge necessary for the participant to feel sensation (perception threshold) and the minimum charge that becomes uncomfortable (discomfort threshold). We will also record the location and quality of the sensation felt at each threshold

  Postoperatively at each experimental visit at 3,6,9 & 12 months

Study Arms (1)

Regenerative Peripheral Nerve Interface (RPNI)

EXPERIMENTAL

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.

Device: Intramuscular electrodes

Interventions

Intramuscular electrodes DEVICE

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

Regenerative Peripheral Nerve Interface (RPNI)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unilateral amputation of the leg proximal to the knee at least 6 months prior to enrollment.
• Low surgical risk (American Society of Anesthesiologists Class I and II).
• Amputee Mobility Predictor with prosthesis (AMPPRO) score of at least 37 (Gailey et al. 2002).
• Sufficient clearance to a motorized prosthetic leg without the necessity for shoe lifts or extenders on the contralateral limb.

You may not qualify if:

• Severe pain syndrome including complex regional pain syndrome or severe phantom pain. All of these conditions would suggest pathological activity of the nerve and would exclude the participant from participation.
• Untreated mental health disorders and if they have any DSM-5 diagnoses, they must receive approval to participate from their mental health professional.
• Any medical conditions that, in the opinion of the Principal Investigator, would place them at high risk for a surgical procedure including recent myocardial infarction, cerebrovascular accidents, deep venous thrombosis, pulmonary embolus, uncontrolled diabetes, or end stage renal disease.
• Participants must not have used tobacco for at least one month prior to enrollment in the study.
• Participants must agree to not use tobacco for the duration of the study.
• Pregnancy.
• No other indwelling electronic implants like pacemakers, implantable cardioverter defibrillators, implantable neurostimulators, body worn insulin pumps, or body worn patient monitoring devices.
• Severe peripheral vascular occlusive disease, venous hypertension of the extremity, or severe lymphedema of the extremity.
• An autoimmune condition which is not well controlled by medication.
• A significant injury of the contralateral limb.
• Significant, uncorrected vision problems.
• Impaired mental capacity that negatively impacts verbal communication with the clinicians and research team or requires a Legally Authorized Representative to facilitate communication.

Sponsors & Collaborators

• University of Michigan: lead
• United States Department of Defense: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Study Officials

• Deanna Gates, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deanna Gates, PhD

CONTACT

734-647-2698; gatesd@umich.edu

Jennifer B Hamill, MPH

CONTACT

570.559.7912; jenberry@umich.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, School of Kinesiology

Study Record Dates

• First Submitted: February 9, 2024
• First Posted: February 23, 2024
• Study Start: February 13, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)