Prosthesis With Sensations

Study Overview
=================
Brief Summary
-----------------
Lower limb amputees suffer complete lack of sensory feedback of current available prostheses, which excludes the central nervous system from the correct sensory-motor integration. It causes serious problems as: falls due to unexpected perturbations, asymmetric walking, low mobility, higher power consumption, feeling the prosthesis as a foreign body, high cognitive burden, and phantom limb pain occurrence. Investigators will provide amputees with a prosthesis restoring sensory feedback and will assess its benefits on the users.

Detailed Description
-----------------
The clinical investigation described here aims at evaluating the benefit of a lower limb prosthesis providing sensory feedback (bidirectional prosthesis), in selected transfemoral amputees. The device is constituted by i) Rheo Knee XC, Pro Flex foot and customized socket/liner structure from OSSUR. Rheo Knee embedded already an encoder coupled with a Bluetooth unit, which is used to make communication with devices external to the knee itself; ii) nerve stimulating system constituted by implantable intraneural electrodes from IMTEK, iii) an external neurostimulator from AXONIC, and iv) sensorized sole from SensArs Neuroprosthetics to apply under the prosthetic foot and driving the stimulating system. The readout of the sensorized insole are transmitted via Bluetooth, together with the encoder readout, to an external controller, which transduces it in parameters of stimulation. These parameters are sent to the stimulator, which injects current into the intraneural electrodes. As final result, the subject perceives sensory feedback from the prosthesis when using it. Investigators call SENSY the sensory feedback restoration system. The subjects will use the prosthesis with and without sensory feedback to execute walking tasks. The average change of kinematics (including falls), metabolic cost, embodiment, and cognitive burden (EEG) when intraneural stimulation is provided will be compared to the case in which there is no sensory feedback. Standard clinical tests (as PEQ and CB&MS) will be executed with and without sensory feedback. Also, when the subjects will report attacks of phantom pain, they will undergo a 10-minutes-stimulation session. Only stimulation without prosthesis is used in this intervention. Finally, imaging of the cortical activity will be executed through functional magnetic resonance imaging (fMRI). This procedure will be only observational since no prosthesis or sensory feedback will be used by the subjects.

Official Title
-----------------
Restoration of Sensations From the Lost Limb to Amputees for Fall Avoidance, Regular Walking, Phantom Limb Pain Diminishment and Embodiment of Prosthesis

Conditions
-----------------
Amputation, Phantom Limb Pain, Sensory Deficit

Intervention / Treatment
-----------------
* Device: SENSY


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Uni-lateral transfemoral amputation above the knee level Other treatments for phantom limb pain should have been tried with poor results The subject should experience phantom limb pain at a level of 6 or higher measured on on a visual analog scale (VAS) ranging from 0-10 Phantom limb pain should be experienced at least once a week The subject should be in a chronic and stable phase, and the stump should have healed The subject should otherwise be healthy and able to carry out the experiment If pain medication is used it will be acceptable that the person continues to use the medication Exclusion Criteria: Cognitive impairment Pregnancy Prior or current psychological diseases such as borderline, schizophrenia, depression or maniodepression Acquired brain injury with residual impairment Prior neurological or musculoskeletal diseases History of or active substance abuse disorder Excessive sensitivity to electrical stimulation with surface electrodes Persons with fear for electrical stimulation, pain cannot participate Persons that are hypersensitive to electrical stimulation and experience the stimulation as unpleasant cannot participate Since the protocol includes MRI scanning of the brain, persons that may feel claustrophobic cannot participate

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SENSY benefit<br>Sensory feedback elicited by intraneural stimulation will be provided by SENSY with and without the leg prosthesis to improve walking ability, increase embodiment, and reduce metabolic cost, cognitive load and phantom pain. | Device: SENSY<br>* The sensory feedback will be delivered by SENSY with or without the leg prosthesis. Benefits connected to the stimulation of sensory nerves will be assessed.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of SENSY on mobility | Demonstration of statistically relevant increase of kinematic walking speed (distance/minute) during the execution of tests involving the use of the prosthesis with intraneural stimulation compared to without the stimulation (e.g. climbing and descending stairs, tandem walking, walking on an outdoor surface). | within 3 months post implant | 
| Impact of SENSY on falls avoidance | Demonstration of statistically relevant decrease of falls during the execution of tests involving the use of the prosthesis with intraneural stimulation compared to without the stimulation (e.g. walking on a surface with obstacles). | within 3 months post implant | 
| Impact of SENSY on metabolic consumption | Demonstration of statistically relevant decrease of metabolic cost during the execution of tests involving the use of the prosthesis with intraneural stimulation compared to without the stimulation (e.g. walking on the treadmill and walking on an outdoor surface). Metabolic cost is measured as volume of oxygen (VO2) consumption (mLO2/kg/meter). | within 3 months post implant | 
| Incidence of all serious adverse events concerning SENSY | Incidence of all serious adverse events, including Serious Adverse Events, Serious Adverse Device Events, and Unanticipated (Serious) Adverse Device Events from the time of consent through 3 months post implant. | within 3 months post implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of SENSY on phantom pain: neuropathic pain symptom inventory score | Demonstration of statistically relevant reduction in neuropathic pain symptom inventory (NPSI) pain score (0-100) from pre-treatment to post-treatment (10-minutes stimulation session is the treatment). | within 3 months post implant | 
| Impact of SENSY on phantom pain: visual analog scale score | Demonstration of statistically relevant reduction in visual analog scale (VAS) pain score (0-10) from pre-treatment to post-treatment (10-minutes stimulation session is the treatment). | within 3 months post implant | 
| Impact of SENSY on phantom pain before and after the implant of SENSY: NPSI score | Average change in NPSI pain score among 1 day pre-implant, 1 day pre-explant, 1.5 and 3 months after the explant. | until up to 3 months post explant | 
| Impact of SENSY on phantom pain before and after the implant of SENSY: VAS score | Average change in VAS pain score among 1 day pre-implant, 1 day pre-explant, 1.5 and 3 months after the explant. | until up to 3 months post explant | 
| Impact of SENSY on embodiment (perception of the prosthesis as part of the body): questionnaires | Average change of embodiment (measured through questionnaires) after use of the prosthesis with and without intraneural stimulation. | within 3 months post implant | 
| Impact of SENSY on embodiment (perception of the prosthesis as part of the body): proprioceptive drift | Average change of embodiment (measured through proprioceptive drift) after use of the prosthesis with and without intraneural stimulation. | within 3 months post implant | 
| Impact of SENSY on cognitive effort | Average change of cortical burden (measured as electroencephalography (EEG) activity) during use of the prosthesis with and without intraneural stimulation. | within 3 months post implant | 
| Impact of SENSY on cortical plasticity | Average cortical reorganization measured through functional Magnetic Resonance Imaging between after the implant and after the explant. | within 3 months post explant |