Mechanisms of Neurodynamic Treatments

NCT05859412 | Recruiting

• 1 other identifier: 313200
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

INTRODUCTION: Carpal tunnel syndrome (CTS) is a relatively common condition caused by compression of one of the main nerves at the wrist, the median nerve. Non-surgical treatments, like steroid injections and physiotherapy, are the first line of treatment for patients with carpal tunnel syndrome. The investigators have previously shown that specific physiotherapeutic exercises (neurodynamic exercises) can reduce the need for carpal tunnel surgery in some patients. Experimental studies in animal models demonstrate that these exercises have an anti-inflammatory effect and can help the nerve to regenerate. However, the exact mechanisms of action of these exercises are not well understood in patients. A better understanding of the mechanisms of action of physiotherapeutic exercises would help clinicians to better target these treatments to those patients who may benefit from them. AIM: To investigate 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). METHODS AND ANALYSIS: In this single-blind randomised mechanistic trial, patients with confirmed mild to moderate CTS (n=78) and age and gender-matched healthy controls (n=30) will be included. Patients will be randomly allocated to a 6-week neurodynamic exercise group, steroid injection, or advice group. Outcome measures will be explored at baseline (patients and controls), post-intervention (patients), and 6-month follow-up (patients). Outcomes include diffusion-weighted and anatomical MRI of the median nerve at the wrist, quantitative sensory testing, nerve conduction studies, inflammatory markers in blood and skin biopsies, and validated questionnaires for pain, function, and psychological factors. Two-way repeated measures ANCOVAs (factors time and intervention, adjusted for baseline measurements as a continuous covariate) will be performed to identify differences in MRI parameters, clinical assessment, and inflammatory markers between patients in different groups and healthy controls.

Conditions

Carpal Tunnel Syndrome; Neurodynamic Treatment; Nerve Mobilisation; Diffusion MRI; Physiotherapy; Mechanistic Trial

Outcome Measures

Primary Outcomes (2)

• Median nerve fractional anisotropy as determined on diffusion weighted imaging

  Fractional anisotropy will be extracted from regions-of-interest in the median nerve and compared to healthy control group

  Baseline

• Change in median nerve fractional anisotropy as determined on diffusion weighted imaging

  Change in fractional anisotropy extracted from regions-of-interest in the median nerve at post-intervention (after 6-weeks) compared to baseline

  From baseline to post-intervention (after 6-weeks)

Secondary Outcomes (50)

• Nerve markers on diffusion weighted imaging: water diffusivity (mm2/s)

  Baseline

• Change to nerve markers on diffusion weighted imaging: water diffusivity (mm2/s)

  From baseline to post-intervention (after 6-weeks)

• Nerve markers on anatomical MRI

  Baseline

• Change in nerve markers on anatomical MRI

  From baseline to post-intervention (after 6-weeks)

• Median nerve MRI T2 mapping

  Baseline

Other Outcomes (8)

• Blood samples - DNA

  Baseline

• Change in blood samples - DNA

  From baseline to post-intervention (after 6-weeks)

• Concentration of serum inflammatory markers - metabolomics

  Baseline

Study Arms (3)

Neurodynamic exercises

EXPERIMENTAL

6-weeks home exercise programme of nerve and tendon gliding exercises

Other: Neurodynamic exercises

Steroid injection Steroid injection (Depomedrone 40mg)

ACTIVE COMPARATOR

Single steroid injection into Carpal Tunnel (positive control group)

Drug: Steroid injection (Depomedrone 40mg)

Advice

OTHER

The advice group will receive advice but no additional intervention during the 6 week intervention period (negative control group)

Other: Advice

Interventions

Neurodynamic exercises OTHER

The neurodynamic exercises will consist of a home-based exercise programme performed over a period of 6 weeks. Patients will attend a single session with an investigator who will instruct them the home exercise programme consisting of nerve and tendon gliding exercises which will be adjusted with pre-specified progressions over the 6 weeks intervention period. Patients will receive a leaflet and a video link detailing these exercises.

Neurodynamic exercises

Steroid injection (Depomedrone 40mg) DRUG

Steroid injection (Depomedrone 40mg) into the carpal tunnel as per standard practice in patients with carpal tunnel syndrome

Steroid injection Steroid injection (Depomedrone 40mg)

Advice OTHER

Group receiving advice but no additional treatment

Advice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients:
• Patients who have a diagnosis of mild to moderate carpal tunnel syndrome based on a clinical assessment and confirmed with nerve conduction studies.
• Male or Female, aged 18 years or above.
• Patient is willing and able to give informed consent for participation in the study.
• Healthy participants:
• Male or female aged 18 years or above.
• Participant is willing and able to give informed consent for participation in the study.
• No history of hand or arm symptoms
• No history of neck pain in the past 3 months
• No systemic medical condition
• No strong anticoagulant medication or altered coagulation (e.g., hemophilia) preventing skin biopsies
• Severe anxiety or depression
• Participants are required to be age- \& sex-matched to patient participants
• No contraindications for magnetic resonance scanning at 3T
• Sufficient command of the English language

You may not qualify if:

• Patients:
• Patients who already had surgery for their carpal tunnel syndrome (CTS) or are planning to undergo surgery in the next 6 weeks (patients with unilateral surgery who have unoperated CTS on the other hand are eligible to participate)
• Patients who had a steroid injection for their CTS in the 6 months prior to the study enrolment or who had already more than 1 steroid injection into the study wrist.
• Patients who have a diagnosis of severe carpal tunnel syndrome based on a clinical assessment and confirmed with electrodiagnostic testing
• Electrodiagnostic testing revealing abnormalities other than CTS
• Any other upper limb or neck problem for which they have sought treatment in the past 3 months
• History of significant trauma to the upper limb or neck
• Diabetes
• Hypothyroidism
• Severe anxiety or depression
• Patient who is pregnant, lactating, or planning pregnancy during the study.
• Patients on strong anticoagulant medication or altered coagulation preventing skin biopsies.
• Contraindications for magnetic resonance imaging (assessed with MRI safety screening questionnaire).
• Contraindications for steroid injections
• Insufficient command of the English language

Sponsors & Collaborators

• University of Oxford: lead
• Wellcome Trust: collaborator

Study Sites (1)

Nuffield Department of Clinical Neurosciences, University of Oxford

Oxford, Oxfordshire, OX3 9DU, United Kingdom

RECRUITING

Related Publications (1)

• E SS, M T, Ac T, M S, G B, Ab S. Mechanisms of neurodynamic treatments (MONET): a protocol for a mechanistic, randomised, single-blind controlled trial in patients with carpal tunnel syndrome. BMC Musculoskelet Disord. 2024 Jul 27;25(1):590. doi: 10.1186/s12891-024-07713-6.

  PMID: 39068435 DERIVED

MeSH Terms

Conditions

Carpal Tunnel Syndrome

Interventions

Steroids; Counseling

Condition Hierarchy (Ancestors)

Median Neuropathy; Mononeuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Nerve Compression Syndromes; Cumulative Trauma Disorders; Sprains and Strains; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Fused-Ring Compounds; Polycyclic Compounds; Mental Health Services; Behavioral Disciplines and Activities; Community Health Services; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Eva Sierra-Silvestre, PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Annina Schmid, PhD

CONTACT

+44 (0) 1865 223254; annina.schmid@ndcn.ox.ac.uk

Eva Sierra-Silvestre, PhD

CONTACT

+44 (0) 1865 234821; eva.sierra@ndcn.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The outcomes assessor and the person responsible for the statistical analysis will be blinded to the participants' allocation.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: A/Prof, PhD, MMACP

Study Record Dates

• First Submitted: April 20, 2023
• First Posted: May 16, 2023
• Study Start: May 17, 2023
• Primary Completion: February 1, 2025
• Study Completion: April 1, 2026
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: IPD that underlie results of a publication will be shared upon the final publication of the main manuscripts of this study.
• Access Criteria: IPD will be shared upon reasonable request and in line with ethical approval with authors contacting the study investigators.

Locations

GB (1)