Protocol for a phase I trial of a novel synthetic polymernerveconduit 'Polynerve' in participants with sensory digitalnerve injury(UMANC).

Ralph Murphy,Adam Reid,Alessandro Faroni,Jason Wong

doi:10.12688/f1000research.19497.1

Abstract

Background: Peripheral nerve injuries are common, with approximately 9,000 cases in the UK annually. Young working individuals are predominantly affected, leading to significant health and social implications. Functional recovery is often poor with impaired hand sensation, reduced motor function and pain and cold intolerance. Where a nerve gap exists, nerve grafting remains the gold-standard treatment but creates a second surgical site, sensory deficit at the donor site, possible neuroma formation and has limited availability. Current commercially available synthetic and resorbable nerve conduit alternatives are reported to be rigid and inflexible. This study will set out to examine the first-in-man use of a new nerve conduit device 'Polynerve' to repair small nerve gaps in digital sensory nerves of the hand. Polynerve is a degradable co-polymer of poly-ε-caprolactone and poly-l-lactic acid, which is shaped as a cylinder that has greater tensile strength, flexibility and less acidic degradation compared with current commercially available synthetic nerve conduits. In addition, it has a novel micro-grooved internal lumen that aids Schwann cell ingress and alignment to improve nerve regeneration. Methods: In total, 17 eligible participants will be recruited to undergo repair of a transected sensory nerve of the hand using the Polynerve device. All participants that receive the nerve conduit device will be followed for a period of 12 months post-surgery. The primary endpoint is safety of the device and the secondary endpoint is degree of sensory nerve regeneration through the conduit assessed using standard sensory testing (2-PD, WEST monofilament testing and locognosia). Discussion: The 'UMANC' trial is a single-centre UK-based, prospective, unblinded, phase I clinical trial of a novel nerve conduit device. We aim to demonstrate the safety of Polynerve as a synthetic, biodegradable nerve conduit and improve the treatment options available to patients with significant nerve injuries. Registration: Clinicaltrials.gov: NCT02970864; EudraCT:2016-001667-37.

Highlights

Peripheral nerve injuries are a common occurrence, with approximately 9000 cases in the UK occurring each year
In comparison to Neurolac®, Polynerve has greater tensile strength, flexibility and less acidic degradation, whilst the microgrooves on the internal lumen provide a protected environment for ingress of Schwann cells, which align on the micro-patterned grooves and aid subsequent nerve regeneration
Nerves selected for the Phase 1 clinical trial of this device will be small sensory nerves of the hand

Summary

Introduction

Peripheral nerve injuries are a common occurrence, with approximately 9000 cases in the UK occurring each year. Despite advances in microsurgical nerve repair techniques, functional recovery is often poor, and can result in impaired hand sensation, reduced motor function and frequent pain and cold intolerance. Polynerve is a degradable co-polymer of poly-ε-caprolactone and poly-l-lactic acid, which is shaped as a cylinder that has greater tensile strength, flexibility and less acidic degradation compared with current commercially available synthetic nerve conduits. It has a novel micro-grooved internal lumen that aids Schwann cell ingress and alignment to improve nerve regeneration. We aim to demonstrate the safety of Polynerve as a synthetic, biodegradable nerve conduit and improve the treatment options available to patients with version 1

Objectives

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Conclusion