MONET trial

  • Research type

    Research Study

  • Full title

    Mechanisms of neurodynamic treatments (MONET)

  • IRAS ID

    313200

  • Contact name

    Annina Schmid

  • Contact email

    annina.schmid@ndcn.ox.ac.uk

  • Sponsor organisation

    University of Oxford / Research Governance, Ethics and Assurance

  • Clinicaltrials.gov Identifier

    NCT05859412

  • Duration of Study in the UK

    3 years, 3 months, 1 days

  • Research summary

    Physiotherapeutic management is the first-line intervention for patients with entrapment neuropathies including Carpal tunnel syndrome. As part of physiotherapy, neurodynamic interventions are often used to treat patients with peripheral nerve injuries. Neurodynamic interventions are designed to glide the nerve in relation to its surrounding tissue while minimising neural strain. We have recently confirmed their efficacy as part of a combination intervention with education and splinting in a subgroup of CTS. Preclinical models suggest that neurodynamic treatments have an anti-inflammatory effect by reducing proinflammatory cytokines and glial activation. There is also increasing evidence that they may have a pro-regenerative and/or anti-degenerative effect on peripheral nerves. To date though, their exact mechanisms of action remain largely unstudied in humans. A better understanding of how neurodynamic interventions work is an important first step towards personalised medicine and will help target these interventions to the right patients.
    Here, we will use carpal tunnel syndrome (CTS) as a model system of a focal peripheral nerve injury. CTS is not only the most common entrapment neuropathy (prevalence 36 per 10000 person-years), but also an ideal model system as it provides good access to investigations of the affected nerve (e.g., nerve conduction studies, magnetic resonance imaging). We have previously used CTS as a model system to explore the pathophysiology of nerve compression and have demonstrated e.g., the presence of nerve degeneration and regeneration, intraneural and systemic inflammation. Importantly, patients with CTS are routinely treated with steroid injection (a potent anti-inflammatory medication), which has established short term benefits and can therefore serve as a positive control treatment.

    We will perform a single-blind randomised mechanistic trial, investigating the mechanisms of action of 6 weeks neurodynamic treatments on nerve function and structure as well as patient reported outcome measures in patients with CTS compared to a positive control intervention (routine care steroid injection) and a negative control intervention (advice).
    We have chosen the steroid injection as a positive control group, as this treatment has proven anti-inflammatory effects and has also been shown to have short-term benefits. The advice group will serve as a negative control intervention to determine normal changes over time.
    The neurodynamic treatment will consist of our previously developed set of seven nerve and tendon gliding exercises. We have previously shown that they can reduce swelling within the affected median nerve in patients with CTS. In this study, we will explore the mechanisms of effect of these neurodynamic treatments in more detail. This will include their potential effect on microstructural nerve integrity, nerve function and inflammatory markers. These domains will be carefully explored using deep phenotyping methodology including specialised nerve MRI imaging, nerve conduction studies, quantitative sensory testing, cutaneous innervation density in skin biopsies and blood inflammatory markers in addition to patient self-reported outcomes.
    We will also include a healthy control group who will provide normative baseline data on nerve structure, function and inflammatory markers.
    Outcome measures related to nerve structure (e.g., MRI, skin biopsies) and function (e.g., electrodiagnostic testing, sensory testing, questionnaires) will be collected at baseline, as well as at 6 weeks and 6 months follow up.
    A better understanding of the mechanisms of action of neurodynamic treatments is an important first step towards the development of precision physiotherapy. Our results will inform how to target these interventions to specific patient populations.

  • REC name

    South Central - Berkshire Research Ethics Committee

  • REC reference

    22/SC/0377

  • Date of REC Opinion

    8 Nov 2022

  • REC opinion

    Further Information Favourable Opinion