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Summary of project/progress /findings (approx 300 words)
The overall aim of my project is to explore the mechanistic underpinning and first-in-human application of non-invasive, pre-operative electrical nerve stimulation to enhance regeneration of peripheral nerves, using carpal tunnel syndrome as a human model system. In total the project forms a four-year DPhil at the University of Oxford.
My project consists of two stages. First is 12 months of computational modelling to optimise non-invasive stimulation of the median nerve at the wrist. These 12 months are supported by BSSH. Second is the PROSpeCT study (Pre-Operative electrical Stimulation to improve Outcomes after Carpal Tunnel decompression). PROSpeCT is a small mechanistic trial of pre-operative electrical nerve stimulation as a neo-adjunct for patients undergoing carpal tunnel decompression surgery. PROSpeCT is patient and surgeon blind, single centre, randomised, and placebo controlled. The primary outcome is improvement in sensory recovery (cold detection threshold, a measure of small sensory fibre function) at 6 months. Secondary outcomes assess other clinical and biological measures of nerve recovery, including PROMS, motor function, quantitative sensory testing, nerve conduction studies, re-innervation of median nerve innervated skin and structural changes on magnetic resonance neurography. Our recruitment target is 60 patients.
In terms of progress to date on the project:
- Design of a simplified geometric computational model of the wrist
- Design of a detailed anatomical wrist model, based on human MRI data
- Ethics approved and drafted SOP for healthy volunteer testing studies in the University of Oxford to confirm model predictions
- Completion of V1.0 of the PROSpeCT protocol and supporting documents, about to be submitted to sponsor for approval, aiming to open recruitment in January 2024
In terms of training, I have completed the Bristol Oxford Aberdeen Surgical Intervention Trials Course and the University of Oxford’s Department for Continuing Education Clinical Trials Management Course.
In terms of further funding, the BSSH has provided a platform for me to successfully apply for funding totalling just under £500,000 in total value (though a portion of this total is now held in Honorary Fellowships, see below).
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What is the relevance/value of this research to hand surgery?
Peripheral injuries affect all aspects of hand surgical practice. Indeed, hand surgeons perhaps carry greatest responsibility for management of these injuries amongst all medical and surgical specialties. In trauma, around 3% of upper limb injuries are complicated by a nerve injury. In the elective context, hand surgeons are uniquely responsible for managing the most prevalent nerve injuries worldwide: compression neuropathies like carpal tunnel and cubital tunnel syndromes. Despite advances in surgical technique, clinical outcomes following PNI have not improved in several decades. This reality is of obvious concern both to surgeons and to our patients. The BSSH’s recent priority setting partnership with the James Lind Alliance identified improving interventions for peripheral nerve injury as a ‘top 10’ research priority in hand and wrist surgery, highlighting the need for work in the area.
My project focuses on electrical nerve stimulation, the only intervention to have improved nerve regeneration and clinical outcomes in multiple human RCTs. At present, our group and our collaborators in Oxford Functional Neurosurgery and the Nuffield Department of Clinical Neurosciences are the only UK team working in this field. I hope that over the next ten years, the support given by the BSSH will enable us to introduce this low risk, low cost, potentially transformative therapy to patients suffering from carpal tunnel syndrome, cubital tunnel syndrome. and distal nerve transections (e.g. digital nerve). In the longer term, I hope the translate the technology into devastating proximal injuries of the brachial plexus, which currently lack any effect treatment.
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If final report, please provide bullet point list of conclusions/important findings:
N/A, interim report
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Please list presentations based on work performed in this study: None at present
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Please list publications based on work performed in this study: None at present
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Please list any further funding or grant applications (with outcome), which have resulted from the award of this grant:
- University of Oxford John Fell Fund (£35,000): outcome awaited
- MRC Clinical Research Training Fellowship (£328,585): successful
- RCS England One Year Research Fellowship (£50,000): successful, now held as an Honorary Fellowship
- University of Oxford St John’s College Clarendon Scholarship (£54,186): successful, now held as Honorary Scholarship
- University of Oxford Medical Sciences Division / EPSRC Studentship (£27,452): successful, now held as Honorary
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How has this grant awards helped your career development?
The BSSH Research Fellowship has been instrumental to starting my career as a surgeon scientist. The Fellowship has allowed me to begin my DPhil on a potentially transformative therapy, during a narrow window of opportunity. In the short term, BSSH support has enabled me to secure competitive funding for the remainder of my DPhil. In the longer term, the training and development made possible by the Society’s financial support will allow me to develop into a national leader in this field, and hopefully bring electrical nerve stimulation to patients across the UK. I envisage myself eventually running mechanistic and efficacy trials of regenerative therapies in patients with a broad range of nerve injuries, which currently lack effective treatments. In particular, the BSSH’s support of a collaborative project means I am already developing close working relationships with neurosurgeons, basic neuroscientists and clinical trialists, which will allow me to drive large collaborative funding applications in future. The interdisciplinary nature of my supervision prepares me well to explore questions of both mechanistic underpinning and clinical efficacy of new therapies, which will be crucial to maximising patient benefit.
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