Tolerability and Feasibility Pilot Clinical Study of a Large-Diameter Nerve Cap for Protecting and Preserving Terminated Nerve Ends

Study Overview
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Brief Summary
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This pilot study evaluates the tolerability and feasibility of the Axoguard Large-Diameter Nerve Cap (sizes 5-7 mm) for protecting and preserving terminated nerve endings after limb trauma or amputation when immediate attention to the nerve injuries is not possible.

Official Title
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Tolerability and Feasibility Pilot Clinical Study of a Large-Diameter Nerve Cap for Protecting and Preserving Terminated Nerve Ends

Conditions
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Symptomatic Neuroma, Amputation, Chronic Nerve Pain

Intervention / Treatment
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* Device: Axoguard Nerve Cap®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Potential Subjects MUST: Sign and date an IRB-approved written Informed Consent Form prior to initiation of any study procedures; Be an adult male or female ≥ 18 and ≤ 80 years of age; Present for surgery with either: Limb trauma and/or planned amputation of a limb and be candidates who are planned for a secondary nerve surgery such as Targeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI) procedures within 6-12 months from time of amputation, or; A previous amputation and be undergoing surgery to address nerve ends; Have at least one nerve end measuring greater than 4 mm and less than 7 mm in diameter after debridement and hemostasis of the proximal nerve stump; Have sufficient soft tissue available to be adequately covered by the Axoguard Nerve Cap; Be willing and able to comply with all aspects of the treatment and follow-up assessments and to return for all required study visits throughout the study duration. Exclusion Criteria: Potential Subjects MUST NOT: Currently undergoing or are expected to undergo treatment with chemotherapy, radiation therapy, or other known treatment that affects the growth of neural and/or vascular tissues; Have signs and symptoms of chemotherapy-induced peripheral neuropathy from previous chemotherapy; Be immunosuppressed or have planned immunosuppressive therapy during the duration of the study; Current uncontrolled local or systemic infection as indicated by positive blood culture or other pathological indicators of infection; Be contraindicated for soft tissue implants. This includes but is not limited to any pathology that would limit the blood supply to the target area or otherwise compromise healing; Have a life expectancy of less than 15-months; Have a history of or be planning to undergo radiotherapy in the area of the end-neuroma; Have bony exostosis of the affected limb that is not treated at the time of nerve cap placement; Have uncontrolled Type 1 or Type 2 Diabetes Mellitus with HbA1c of 8% or greater or those with diabetic neuropathy in the target area or proximal to the amputation site; Have a history of idiopathic neuropathy/radiculopathy, known sciatica or chronic back pain; Documented history of centralized nerve pain that does not respond to a peripheral nerve block in the affected limb; Have a known allergy to anesthetic agents; Have a known sensitivity to porcine-derived products; Be currently enrolled or have been enrolled in another interventional clinical research study within the past 30 days (at time of consent); or Be deemed unsuitable for inclusion in the study at the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Axoguard Nerve Cap®<br>Active Comparator: Porcine derived extracellular matrix (ECM) based Nerve Termination Device Implantation of appropriate diameter of Axoguard Nerve Cap® (sizes 5-7 mm) at the time of surgery | Device: Axoguard Nerve Cap®<br>* Entubulation of the nerve stump into the Axoguard Nerve Cap® following surgical excision of symptomatic neuroma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Adverse Events (AEs), Serious Adverse Events (SAEs), or Unanticipated Adverse Device Effects (UADEs) | The primary safety endpoint will monitor the nature and incidence of AE's, SAE's and/or UADE's associated with an unplanned revision procedure prior to the planned Targeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI) starting from implantation (operative day) through 15 months depending on whether or not the subject undergoes the secondary TMR or RPNI procedure. | 15 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visual Analog Scale (VAS) For Pain Score through TMR procedure or 12 post-operative months compared to baseline | The Visual Analog Scale (VAS) For Pain is a patient reported outcomes scale whereby the patient indicates his/her current pain level by making a mark on a continuous horizontal 10-centimeter (100 millimeter) line. The distance from the 0 millimeter to the patient's mark corresponds to the amount of pain the subject is currently experiencing. VAS for Pain data are recorded as the number of millimeters from the left of the line to the patients mark across the range of 0-100 millimeters, with 0 millimeter representing no pain and 100 millimeters representing the worst pain imaginable. Final VAS score will be collected either just prior to TMR or RPNI procedure or 12- months post op if subject will not undergo the secondary TMR or RPNI procedure | Week 2, 1, 3, 6, 9 and 12 months | 
| Change in Patient Reported Outcome Measurement Information System (PROMIS®) - Pain Related Measures through TMR or RPNI procedure or 12 post operative months compared to baseline | The Patient Reported Outcome Measurement Information System (PROMIS®) - Pain Related Measures is a set of person-centered measures that evaluates and monitors a patient's physical health and pain. The pain related measures include domains evaluating fatigue, pain intensity, pain interference, sleep Disturbance, and Pain Behavior. Short forms containing fixed sets of 4-10 items or questions are included for each domain. All PROMIS scores are presented as T-scores where the T-score is the standardized score with a mean of 50 (range 20-80) and a standard deviation of 10. Higher scores indicate more of the concept being measured where sometimes the concept is desirable (e.g., physical function) and sometimes this it is undesirable (e.g., fatigue). Final PROMIS® Pain Related Measure will be collected either just prior to TMR or RPNI procedure or 12-months post op if subject will not undergo the secondary TMR or RPNI procedure. | Week 2, 1, 3, 6, 9 and 12 months | 
| Change in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) through TMR or RPNI procedure or 12 post-operative months compared to baseline | In this study, the Work Productivity and Activity Impairment (WPAI:SHP) questionnaire is an instrument to measure impairments in both paid work and unpaid work (leisure/regular activities) due nerve injury post-surgical intervention. It measures (1) absenteeism (work time missed), (2) presenteeism (impairment at work / reduced on-the-job effectiveness), (3) work productivity loss (overall work impairment / absenteeism plus presenteeism), as well as the (4) impairments in unpaid activity because of nerve injury post-surgical intervention during the past seven days. Scores for these 4 measures are expressed as impairment percentages with higher percentage scores indicating greater impairment in than lower percentage scores. Final WPAI:SHP will be collected either at the office visit following the TMR or RPNI procedure or 12-months post op if subject will not undergo the secondary TMR or RPNI procedure | Week 2, 1, 3, 6, 9 and 12 months | 
| Change in Brief Activities Measure for Adults with Upper Limb Amputation (BAM-ULA) through 12 post-operative months compared to baseline | The BAM-ULA is a 10-item observational measure of activity performance. The 10 items are as follows: tuck a shirt in pants, lift a 20-lb bag, open a water bottle, remove a wallet from back pocket, replace the wallet in back pocket, take a gallon of water from the refrigerator and place on the counter (lift gallon jug), pour water from a gallon jug, brush or comb hair, use a fork, and open a door with knob. Items are scored with either a 0 (cannot complete all subtasks) or 1 (can complete all subtasks). Lower scores area associated with greater impairment of activity performance and higher scores are associated with less impairment of activity performance. | 3, 6, 9 and 12 months | 
| Change in Timed Up and Go (TUG) Test for Lower Extremity Amputees through 12 post-operative months compared to baseline | An observational test used to evaluate functional mobility in terms of postural stability, gait, stride length, and sway. Patients wear their regular footwear and can use a walking aid. They are asked to sit in a chair, stand up from that chair, walk to a line on the floor (10 ft. away) at their normal pace, turn around, walk back to the chair at a normal pace, and sit down again. | 3, 6, 9 and 12 months | 
| Change in the 10-Meter Walk Test (10 MWT) for Lower Extremity Amputees through 12 post-operative months compared to baseline | A performance measure used evaluate functional mobility and gait. It assesses walking speed in meters per second over 10-meter distance. | 3, 6, 9 and 12 months | 
| Changes in quantity and class of pain medication use at week 2, 1, 3, 6, 9, 12, and 15 post-operative months comparted to baseline | Quantity and class of pain medication use for subjects who were implanted with the Axoguard Nerve Cap® will be captured during the following visits: Screening (baseline), 2-weeks, 1, 3, 6, 9, 12, and 15 months post-op for comparison to baseline. | Week 2, 1, 3, 6, 9, 12, and 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuroma, Peripheral Nerve Injuries, Peripheral Nervous System Disease, Nerve Pain, Nervous System Diseases, Trauma - Nervous System, Amputation, Nerve Repair, Surgical Treatment of Pain