AmputationNCT06275282
Regenerative Peripheral Nerve Interface for Control of Lower Limb Prostheses
A study testing Intramuscular electrodes in people with Amputation and Prostheses and Implants, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amputation, Prostheses and Implants
- What is being tested?
- Intramuscular electrodes
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2025to 30 Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- For participants without existing RPNI grafts (at the time of enrollment), the residual limb must have sufficient soft tissue quality to support performance of the RPNI operative procedures. Participants sustaining severe crushing or avulsion injuries with substantial superficial and deep scarring may not be appropriate candidates for inclusion in the study.
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Deanna Gates, PhD, 723-647-2698, gatesd@umich.edu
Deanna Gates, PhD
About this study
Official title: Regenerative Peripheral Nerve Interfaces to Enhance Function and Sensation in People With Transfemoral Amputation
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:
Read more
- Can the amplitude, movement specificity and stability of sciatic nerve RPNI electromyography (EMG) signals be detected up to one year post RPNI surgery?
- Do RPNIs contain information to enable control of a physical motorized prosthetic leg with multiple degrees of freedom?
- Does stimulation of sciatic nerve RPNIs provides meaningful sensory feedback?
Consenting participants with unilateral transfemoral amputation (TFA) will:
- Undergo RPNI surgery and electrode implantation in the residual limb.
- 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.
- Undergo explantation of electrodes following the conclusion of data collection.
Read the detailed description
Background: While many prosthetic devices have been developed for functional restoration after major lower extremity amputation, there is no stable interface to provide reliable, long-term volitional control of an advanced robotic limb capable of multiple degrees of freedom. Moreover, there is no existing interface that provides useful sensory feedback that in turn enhances the functional capabilities of the prosthesis. To address these limitations, the investigators propose use of a novel 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. As the nerve grows, it reinnervates the free muscle graft which undergoes a predictable sequence of revascularization and regeneration. The RPNI leverages these biological processes to provide three essential benefits to people with amputation: 1) intuitive motor control, 2) sensory feedback, and 3) reduction of post-amputation pain.
Objective/Hypotheses: The objective of this application is to (1) determine the extent to which the RPNIs enable generation of high-fidelity motor control signals for a powered knee-ankle prosthesis and (2) demonstrate that meaningful sensory feedback can be generated from stimulation of sciatic nerve RPNIs.
Specific Aims: The specific aims are to: (1) Evaluate the amplitude, movement specificity and stability of sciatic nerve RPNI electromyography (EMG) signals up to one year post RPNI surgery, (2) Assess functional movement performance using sciatic nerve RPNI signals for control of a physical motorized prosthetic leg with multiple degrees of freedom, and (3) Determine whether stimulation of sciatic nerve RPNIs provides meaningful sensory feedback.
Study design: This project is the first clinical investigation of RPNIs in people with lower-limb amputation. The study will recruit 3 individuals with transfemoral amputation. RPNIs will be surgically constructed on the sciatic nerve and intramuscular electrodes will be implanted into these RPNIs and residual muscles. Experiments will then be conducted at regular intervals up to one year post RPNI surgery. These experiments will measure the EMG signals generated by RPNIs in response to volitional movement of the phantom limb. These signals will then be used to control a two-joint powered prosthesis during cyclic and unpredictable movements. Functional movement, pain, and other patient-reported outcomes will be collected for data analysis. Additionally, RPNIs will be electrically stimulated to elicit sensation. Stimulation will also be provided during the performance of functional tasks.
At the completion of data collection, participants will undergo electrode explantation and complete a postoperative visit to assess recovery, pain and any associated adverse events.
- Conditions
- Amputation, Prostheses and Implants
- Being tested
- Intramuscular electrodes
- Keywords
- RPNI, Regenerative Peripheral Nerve Interface, Implanted Electrodes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intramuscular electrodesDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Intramuscular electrodes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intensity of pain in residual and phantom limbs
Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity-Short Form 3a
Measured: through study completion, an average of 1 year
Neuropathic Pain in residual limb
Leeds Assessment of Neuropathic Symptoms and Signs (LANSS)
Measured: 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)
Measured: 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.
Measured: 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
Measured: 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
Measured: Postoperatively at each experimental visit at 3,6,9 & 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2024
- Study start13 Feb 2025
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AmputationStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Deanna H Gates, University of Michigan
- Investigators
- Deanna Gates, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06275282
- Sponsor's protocol ID
- HUM00235849
- Status last verified
- May 2026
- First submitted
- 9 Feb 2024
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regenerative Peripheral Nerve Interfaces to Enhance Function and Sensation in People With Transfemoral Amputation
- ClinicalTrials.gov ID
- NCT06275282
- Acronym / sponsor ID
- HUM00235849
- Conditions
- Amputation, Prostheses and Implants
- Keywords
- RPNI, Regenerative Peripheral Nerve Interface, Implanted Electrodes
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 3 participants (estimated)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 13 Feb 2025 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 23 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Can the amplitude, movement specificity and stability of sciatic nerve RPNI electromyography (EMG) signals be detected up to one year post RPNI surgery?
- Do RPNIs contain information to enable control of a physical motorized prosthetic leg with multiple degrees of freedom?
- Does stimulation of sciatic nerve RPNIs provides meaningful sensory feedback?
Consenting participants with unilateral transfemoral amputation (TFA) will:
- Undergo RPNI surgery and electrode implantation in the residual limb.
- 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.
- Undergo explantation of electrodes following the conclusion of data collection.
Detailed description
Background: While many prosthetic devices have been developed for functional restoration after major lower extremity amputation, there is no stable interface to provide reliable, long-term volitional control of an advanced robotic limb capable of multiple degrees of freedom. Moreover, there is no existing interface that provides useful sensory feedback that in turn enhances the functional capabilities of the prosthesis. To address these limitations, the investigators propose use of a novel 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. As the nerve grows, it reinnervates the free muscle graft which undergoes a predictable sequence of revascularization and regeneration. The RPNI leverages these biological processes to provide three essential benefits to people with amputation: 1) intuitive motor control, 2) sensory feedback, and 3) reduction of post-amputation pain.
Objective/Hypotheses: The objective of this application is to (1) determine the extent to which the RPNIs enable generation of high-fidelity motor control signals for a powered knee-ankle prosthesis and (2) demonstrate that meaningful sensory feedback can be generated from stimulation of sciatic nerve RPNIs.
Specific Aims: The specific aims are to: (1) Evaluate the amplitude, movement specificity and stability of sciatic nerve RPNI electromyography (EMG) signals up to one year post RPNI surgery, (2) Assess functional movement performance using sciatic nerve RPNI signals for control of a physical motorized prosthetic leg with multiple degrees of freedom, and (3) Determine whether stimulation of sciatic nerve RPNIs provides meaningful sensory feedback.
Study design: This project is the first clinical investigation of RPNIs in people with lower-limb amputation. The study will recruit 3 individuals with transfemoral amputation. RPNIs will be surgically constructed on the sciatic nerve and intramuscular electrodes will be implanted into these RPNIs and residual muscles. Experiments will then be conducted at regular intervals up to one year post RPNI surgery. These experiments will measure the EMG signals generated by RPNIs in response to volitional movement of the phantom limb. These signals will then be used to control a two-joint powered prosthesis during cyclic and unpredictable movements. Functional movement, pain, and other patient-reported outcomes will be collected for data analysis. Additionally, RPNIs will be electrically stimulated to elicit sensation. Stimulation will also be provided during the performance of functional tasks.
At the completion of data collection, participants will undergo electrode explantation and complete a postoperative visit to assess recovery, pain and any associated adverse events.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regenerative Peripheral Nerve Interface (RPNI) | Experimental | Device: Intramuscular electrodesParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
- For participants without existing RPNI grafts (at the time of enrollment), the residual limb must have sufficient soft tissue quality to support performance of the RPNI operative procedures. Participants sustaining severe crushing or avulsion injuries with substantial superficial and deep scarring may not be appropriate candidates for inclusion in the study.
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intramuscular electrodesParticipants 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. | Device | Regenerative Peripheral Nerve Interface (RPNI) |
Primary outcome
Intensity of pain in residual and phantom limbs
Time frame: through study completion, an average of 1 year
Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity-Short Form 3a
Neuropathic Pain in residual limb
Time frame: through study completion, an average of 1 year
Leeds Assessment of Neuropathic Symptoms and Signs (LANSS)
Health-Related Quality of Life
Time frame: through study completion, an average of 1 year
Participants will complete the RAND 36-Item Short Form Health Survey (SF-36)
Amplitude and signal-to-noise ratio for each RPNI
Time frame: Postoperatively at each experimental visit at 3,6,9 & 12 months
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.
Classification accuracy for movements of the phantom limb
Time frame: Postoperatively at each experimental visit at 3,6,9 & 12 months
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
Threshold for sensation after electrical stimulation of RPNI
Time frame: Postoperatively at each experimental visit at 3,6,9 & 12 months
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Deanna Gates, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intramuscular electrodes in people with Amputation and Prostheses and Implants, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Deanna Gates, PhD (734-647-2698, gatesd@umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intensity of pain in residual and phantom limbs (time frame: through study completion, an average of 1 year). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.