Upper Limb AmputeesPSINCT04947462
Proprioceptive Sensorimotor Integration With Neural Interfaces for Hand Prostheses
A study testing Chronically Implanted Neural and Muscular Interface in people with Upper Limb Amputees, run by VA Office of Research and Development at 1 site in United States.
Trial summary
The purpose of this study is to characterize proprioceptive sensations in the missing limb of upper limb amputees using nerve stimulation, and to develop advanced controllers for moving a prosthesis. Proprioceptive sensations are the sensations that tell individuals where their hand is in space, and if it is moving. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Upper Limb Amputees
- What is being tested?
- Chronically Implanted Neural and Muscular Interface
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2021to 31 May 2030
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Veteran
- Unilateral upper limb amputation above or below the elbow with fully healed and healthy surgical sites
- Viable peripheral nerve function in the residual nerves serving the limb
- Volitional activity of the residual muscles in the amputated limb or actuating movement of the limb
- Medically fit to undergo general anesthesia
- Fitted with a prosthesis by a certified prosthetic and orthotic specialist (CPO) and at least one month of experience using a prosthesis
- Willingness and availability to follow the study protocol
- Willingness to undergo psychological evaluation, if recommended by study surgeons or investigators, to determine that the participant is mentally competent and capable of completing the study-related activities
Who cannot join
- Bilateral upper limb amputation, unless the amputation on the contralateral side only involves missing digits but does not qualify as a partial hand amputation
- Inability to speak English
- Medically unfit to undergo surgery
- Pregnancy, or those who are of childbearing potential, unwilling to prevent pregnancy during the trial
- Uncontrolled diabetes (Hemoglobin A1c (HgbA1c)>8.0%)
- History of neuropathy and/or radiculopathy in the target limb
Show all 11Show fewer
- Active infection or open sores on the residual limb
- History of frequent infection or sores with unknown cause
- Inability to provide informed consent or follow experimental protocols
- Severe pain that would prevent the participant from completing study-related activities
- Poor surgical candidate
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
Louis Stokes VA Medical Center, Cleveland, OH
Cleveland, Ohio, 44106-1702
Jessica R Jarvela, MS BS, (216) 791-3800 ext. 63801, Jessica.Jarvela@va.gov
Melissa S Schmitt, (216) 791-3800 ext. 63801, Melissa.Schmitt@va.gov
About this study
The purpose of this study is to characterize proprioceptive sensations in the missing limb of upper limb amputees using nerve stimulation, and to develop advanced controllers for moving a prosthesis. Proprioceptive sensations are the sensations that tell individuals where their hand is in space, and if it is moving. The research team uses Functional Electrical Stimulation (FES), which involves applying small electric currents to the nerves. These signals are then transferred to the brain just like the information about the individual's intact hand used to be transferred to their brain. This study will test different placements for stimulation and determine which one(s) provide the individual with proprioceptive sensations. The investigators want to know what the participants feel and if the investigators can use proprioceptive sensation to give the participants information about limb movement and position.
Read the detailed description
Hands are the primary means of interacting with the world, and Veterans who have lost a hand must cope with diminished functional and sensory capabilities. While myoelectric prostheses can restore the basic grasping function of the lost hand, many amputees abandon use of prostheses because current prosthetic options do not meet their needs. In addition, many amputees struggle with phantom pain and psychosocial deficits following limb loss that are not fully mitigated by current treatments.
In the normal sensorimotor system, proprioception, which is the sense of limb position and movement, is critical for informing motor plans and correcting errors in movement. In addition, proprioception plays a key role in body ownership, agency, and phantom pain. Despite its importance, proprioception is absent in current prosthetic options.
The goal of the proposed project is to make upper limb prosthetic devices more natural and useful for Veterans who have lost a hand by providing proprioceptive feedback about prosthesis postures and movements. The central hypothesis is that effectively closing the loop between a prosthesis user and their device requires that the sensory inputs and control outputs closely mimic the underlying sensorimotor neural processes of the body schema. The investigators will examine integration of artificial proprioception with prosthesis control in eight trans-radial or four trans-humeral amputees using the investigators' implanted neural-interfacing system and intramuscular EMG.
Aim 1. Characterize proprioceptive sensations elicited by peripheral nerve stimulation. The investigators will test time-varying Peripheral Nerve Stimulation (PNS) patterns and examine the impact on the kinematics of the evoked proprioceptive percept using position matching with the contralateral intact limb and multivariate regression analyses. The investigators will investigate paired agonist-antagonist stimulation strategies and compare the discriminability between agonist-only and paired agonist-antagonist strategies using psychometric tests. As well as assess the psychometric properties of PNS-evoked proprioceptive percepts and examine the interaction of proprioception with concurrent touch feedback and voluntary muscle contraction.
Aim 2. Investigate the mechanisms of stimulation-evoked proprioception. The neurophysiological basis of proprioception from PNS is unknown. To investigate whether proprioceptive percepts originate from direct afferent activation or indirect recruitment via direct muscle activation, the investigators will perform a motor block of the residual forearm of trans-radial participants and examine changes to the proprioceptive percepts. In trans-humeral participants, Targeted Muscle Reinnervation will be performed at the time of system implant, and percepts will be compared before and after muscle ingrowth.
Aim 3. Determine the integration of proprioceptive stimulation with motor control during posture matching. To restore proprioception to Veterans during active prosthesis use, PNS-evoked percepts must be integrated with voluntary limb control. The investigators will determine the impact of proprioception on motor control through a virtual reality posture matching task and compare performance with velocity and position-based prosthetic hand controllers with and without proprioceptive PNS. The investigators will determine the impact of voluntary control on the perception of PNS-evoked proprioception through a psychometric dissimilarity rating task. The investigators will assess the impact of artificial proprioception on embodiment via surveys. The investigators will also explore how control of multi-DOF movements with intramuscular EMG signals can be decoded via machine learning (ML)-based controllers by comparing the integration of proprioception with machine learning-based velocity control vs machine learning-based position control in virtual hand posture matching tasks. Investigators will access this impact by having the participants perform functional tasks in the laboratory with the best performing controller and a multi-DOF prosthetic hand with joint position sensors.
The project will be the first to investigate the sensorimotor integration of proprioception from PNS in a broad population of upper-limb amputees and with both position and velocity controllers. The study will provide important information about the kinematics of artificial proprioception and the role of direct muscle activation in forming proprioceptive percepts. The investigators expect that knowledge gained in this proposal will improve prosthesis utility and acceptance for Veterans with limb loss and will advance prosthetic hand technology and standard of care in the neurorehabilitation field.
- Conditions
- Upper Limb Amputees
- Being tested
- Chronically Implanted Neural and Muscular Interface
- Keywords
- Proprioception, Prosthesis, Upper Extremity Limb Loss, Peripheral Nerve Stimulation, Embodiment, Sensorimotor, Neuroprostheses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chronically Implanted Neural and Muscular InterfaceDevice
Participants will be chronically implanted with neural and muscular interfaces to characterize proprioceptive sensations using Functional Electrical Stimulation (FES).
| Study group | Role | What they receive |
|---|---|---|
| Chronically Implanted Neural and Muscular Interface | Experimental | 8 eligible participants will be chronically implanted with neural and muscular interfaces to characterize proprioceptive sensations using Functional Electrical Stimulation (FES). Receives: Device: Chronically Implanted Neural and Muscular Interface |
What is being measured
The primary outcome is the main question the study is designed to answer.
Magnitude of change in perceived joint position
Magnitude of change in perceived joint position, as measured by joint angle transducers in the Cyberglove. As well as just noticeable difference (JND) of perceived magnitude, JND of perceived frequency, temporal detection threshold (TDT), and adaptation time constants for proprioceptive percepts
Measured: This metric will be measured approximately each month for two years.
Secondary outcomes (2)
Multi-Dof posture matching
Participants will perform a multi-DOF posture matching task in virtual reality, where they will be asked to control multiple DOF simultaneously to achieve a multi-DOF target posture. Each controlled DOF will have a matched proprioceptive percept, and the number of DOF controlled in this task will be 2-4. Trial time will be the primary metric measure.
Measured: This metric will be measured approximately each month for two years.
Object Discrimination
The participant will complete object discrimination tasks and simulated activities of daily living both with and without proprioceptive feedback. Identification accuracy will be the primary metric measure
Measured: This metric will be measured approximately each month for two years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2021
- Study start1 Dec 2021
- Primary completion31 May 2030 (estimated)
- Study completion31 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Upper Limb AmputeesStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Emily L Graczyk, PhD, Principal investigator, Louis Stokes VA Medical Center, Cleveland, OH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04947462
- Sponsor's protocol ID
- A3699-R
- Other IDs
- RX003699-01, 1624763, 1I01RD000699-01A2
- Acronym
- PSI
- Status last verified
- Aug 2026
- First submitted
- 23 Jun 2021
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Wright JD, Charkhkar H, Graczyk EL. Mind the gap: the temporal discrimination threshold of tactile sensation from implanted peripheral nerve stimulation. J Neuroeng Rehabil. 2026 Apr 18;23(1):179. doi: 10.1186/s12984-026-01986-9.
PubMed 42001150
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proprioceptive Sensorimotor Integration With Neural Interfaces for Hand Prostheses
- ClinicalTrials.gov ID
- NCT04947462
- Acronym / sponsor ID
- PSI / A3699-R
- Conditions
- Upper Limb Amputees
- Keywords
- Proprioception, Prosthesis, Upper Extremity Limb Loss, Peripheral Nerve Stimulation, Embodiment, Sensorimotor, Neuroprostheses
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 31 May 2030 (estimated)
- Study completion
- 31 May 2030 (estimated)
- First posted
- 1 Jul 2021 (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.
The purpose of this study is to characterize proprioceptive sensations in the missing limb of upper limb amputees using nerve stimulation, and to develop advanced controllers for moving a prosthesis. Proprioceptive sensations are the sensations that tell individuals where their hand is in space, and if it is moving. The research team uses Functional Electrical Stimulation (FES), which involves applying small electric currents to the nerves. These signals are then transferred to the brain just like the information about the individual's intact hand used to be transferred to their brain. This study will test different placements for stimulation and determine which one(s) provide the individual with proprioceptive sensations. The investigators want to know what the participants feel and if the investigators can use proprioceptive sensation to give the participants information about limb movement and position.
Detailed description
Hands are the primary means of interacting with the world, and Veterans who have lost a hand must cope with diminished functional and sensory capabilities. While myoelectric prostheses can restore the basic grasping function of the lost hand, many amputees abandon use of prostheses because current prosthetic options do not meet their needs. In addition, many amputees struggle with phantom pain and psychosocial deficits following limb loss that are not fully mitigated by current treatments.
In the normal sensorimotor system, proprioception, which is the sense of limb position and movement, is critical for informing motor plans and correcting errors in movement. In addition, proprioception plays a key role in body ownership, agency, and phantom pain. Despite its importance, proprioception is absent in current prosthetic options.
The goal of the proposed project is to make upper limb prosthetic devices more natural and useful for Veterans who have lost a hand by providing proprioceptive feedback about prosthesis postures and movements. The central hypothesis is that effectively closing the loop between a prosthesis user and their device requires that the sensory inputs and control outputs closely mimic the underlying sensorimotor neural processes of the body schema. The investigators will examine integration of artificial proprioception with prosthesis control in eight trans-radial or four trans-humeral amputees using the investigators' implanted neural-interfacing system and intramuscular EMG.
Aim 1. Characterize proprioceptive sensations elicited by peripheral nerve stimulation. The investigators will test time-varying Peripheral Nerve Stimulation (PNS) patterns and examine the impact on the kinematics of the evoked proprioceptive percept using position matching with the contralateral intact limb and multivariate regression analyses. The investigators will investigate paired agonist-antagonist stimulation strategies and compare the discriminability between agonist-only and paired agonist-antagonist strategies using psychometric tests. As well as assess the psychometric properties of PNS-evoked proprioceptive percepts and examine the interaction of proprioception with concurrent touch feedback and voluntary muscle contraction.
Aim 2. Investigate the mechanisms of stimulation-evoked proprioception. The neurophysiological basis of proprioception from PNS is unknown. To investigate whether proprioceptive percepts originate from direct afferent activation or indirect recruitment via direct muscle activation, the investigators will perform a motor block of the residual forearm of trans-radial participants and examine changes to the proprioceptive percepts. In trans-humeral participants, Targeted Muscle Reinnervation will be performed at the time of system implant, and percepts will be compared before and after muscle ingrowth.
Aim 3. Determine the integration of proprioceptive stimulation with motor control during posture matching. To restore proprioception to Veterans during active prosthesis use, PNS-evoked percepts must be integrated with voluntary limb control. The investigators will determine the impact of proprioception on motor control through a virtual reality posture matching task and compare performance with velocity and position-based prosthetic hand controllers with and without proprioceptive PNS. The investigators will determine the impact of voluntary control on the perception of PNS-evoked proprioception through a psychometric dissimilarity rating task. The investigators will assess the impact of artificial proprioception on embodiment via surveys. The investigators will also explore how control of multi-DOF movements with intramuscular EMG signals can be decoded via machine learning (ML)-based controllers by comparing the integration of proprioception with machine learning-based velocity control vs machine learning-based position control in virtual hand posture matching tasks. Investigators will access this impact by having the participants perform functional tasks in the laboratory with the best performing controller and a multi-DOF prosthetic hand with joint position sensors.
The project will be the first to investigate the sensorimotor integration of proprioception from PNS in a broad population of upper-limb amputees and with both position and velocity controllers. The study will provide important information about the kinematics of artificial proprioception and the role of direct muscle activation in forming proprioceptive percepts. The investigators expect that knowledge gained in this proposal will improve prosthesis utility and acceptance for Veterans with limb loss and will advance prosthetic hand technology and standard of care in the neurorehabilitation field.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chronically Implanted Neural and Muscular Interface | Experimental | Device: Chronically Implanted Neural and Muscular Interface8 eligible participants will be chronically implanted with neural and muscular interfaces to characterize proprioceptive sensations using Functional Electrical Stimulation (FES). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Veteran
- Unilateral upper limb amputation above or below the elbow with fully healed and healthy surgical sites
- Viable peripheral nerve function in the residual nerves serving the limb
- Volitional activity of the residual muscles in the amputated limb or actuating movement of the limb
- Medically fit to undergo general anesthesia
Key exclusion criteria (11 listed)
- Bilateral upper limb amputation, unless the amputation on the contralateral side only involves missing digits but does not qualify as a partial hand amputation
- Inability to speak English
- Medically unfit to undergo surgery
- Pregnancy, or those who are of childbearing potential, unwilling to prevent pregnancy during the trial
- Uncontrolled diabetes (Hemoglobin A1c (HgbA1c)>8.0%)
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 |
|---|---|---|
| Chronically Implanted Neural and Muscular InterfaceParticipants will be chronically implanted with neural and muscular interfaces to characterize proprioceptive sensations using Functional Electrical Stimulation (FES). | Device | Chronically Implanted Neural and Muscular Interface |
Primary outcome
Magnitude of change in perceived joint position
Time frame: This metric will be measured approximately each month for two years.
Magnitude of change in perceived joint position, as measured by joint angle transducers in the Cyberglove. As well as just noticeable difference (JND) of perceived magnitude, JND of perceived frequency, temporal detection threshold (TDT), and adaptation time constants for proprioceptive percepts
2 secondary outcomes
Multi-Dof posture matching
Time frame: This metric will be measured approximately each month for two years.
Object Discrimination
Time frame: This metric will be measured approximately each month for two years.
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 21 Aug 2026.
- Derived from this study: PubMed 42001150Wright JD, Charkhkar H, Graczyk EL. Mind the gap: the temporal discrimination threshold of tactile sensation from implanted peripheral nerve stimulation. J Neuroeng Rehabil. 2026 Apr 18;23(1):179. doi: 10.1186/s12984-026-01986-9.
- E. Gardner, J. Martin, in Principles of neural science (2000;Link provided by the sponsor.
- 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.
Emily L Graczyk, PhD principal investigator
Louis Stokes VA Medical Center, Cleveland, OH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chronically Implanted Neural and Muscular Interface in people with Upper Limb Amputees, run by VA Office of Research and Development 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 8 inclusion and 11 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 21 Aug 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 Emily L Graczyk, PhD ((216) 791-3800 ext. 63571, Emily.Graczyk@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Magnitude of change in perceived joint position (time frame: This metric will be measured approximately each month for two years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04947462, which also lists 1 linked publication.
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 21 Aug 2026.