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NCT Number: NCT05859412

Mechanisms of Neurodynamic Treatments

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.

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Key information

Conditions

Carpal Tunnel Syndrome Cumulative Trauma Disorders Diffusion MRI Mechanistic Trial Median Neuropathy Mononeuropathies Nerve Compression Syndromes Nerve Mobilisation Nervous System Diseases Neurodynamic Treatment Neuromuscular Diseases Peripheral Nervous System Diseases Physiotherapy Sprains and Strains Wounds and Injuries

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Nuffield Department of Clinical Neurosciences, University of Oxford

Oxford, Oxfordshire, OX3 9DU, United Kingdom

About this study

Follow-up at 6 months will only include outcome measures from questionnaires.

Details on enrollment:

Pilot testing of healthy participants who consented to our ethics but will not be included in the study was on 13-April-2023.

  • First healthy participant enrolled: 17-May-2023.
  • First patient participant enrolled: 1-June-2023.

Details on amendment:

  • Amendment SA2_BPOR on 3/Aug/2023 to expand recruitment through registries of patients
  • Amendment SA3_REC on 22/Aug/2023 to add Thames Valley Primary Care Research Partnership, musculoskeletal clinics, and media advertisement to help with recruitment of participants.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

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.

Steroid injection (Depomedrone 40mg)

Drug

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

Advice

Other

Group receiving advice but no additional treatment

Primary outcomes

  1. Median nerve fractional anisotropy as determined on diffusion weighted imaging

    Time frame: Baseline

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

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

    Time frame: From baseline to post-intervention (after 6-weeks)

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

Secondary outcomes

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

    Time frame: Baseline

    Measured at the median nerve and cervical dorsal root ganglia. mm2/s; continuous data

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

    Time frame: From baseline to post-intervention (after 6-weeks)

    Measured at the median nerve and cervical dorsal root ganglia. mm2/s; continuous data

  3. Nerve markers on anatomical MRI

    Time frame: Baseline

    Measured at the median nerve and cervical dorsal root ganglia. ratio/mm2; continuous data

  4. Change in nerve markers on anatomical MRI

    Time frame: From baseline to post-intervention (after 6-weeks)

    Measured at the median nerve and cervical dorsal root ganglia. ratio/mm2; continuous data

  5. Median nerve MRI T2 mapping

    Time frame: Baseline

    ms; continuous data

  6. Changes in median nerve MRI T2 mapping

    Time frame: From baseline to post-intervention (after 6-weeks)

    ms; continuous data

  7. Median nerve MRI magnetisation transfer ratio (MTR)

    Time frame: Baseline

    ratio; continuous data

  8. Changes in median nerve MRI magnetisation transfer ratio (MTR)

    Time frame: From baseline to post-intervention (after 6-weeks)

    ratio; continuous data

  9. Changes in median nerve conduction velocities from electrodiagnostic studies (m/s)

    Time frame: From baseline to post-intervention (after 6-weeks)

    m/s; continuous data

  10. Changes in median sensory nerve action potentials (SNAPs) and compound muscle action potentials (CMAPs): amplitudes (mV)

    Time frame: From baseline to post-intervention (after 6-weeks)

    mV; continuous data

  11. Thermal detection thresholds as assessed in Quantitative Sensory testing - warm and cold detection threshold; thermal sensory limen

    Time frame: Baseline

    Thermal detection thresholds will be assessed using a thermode over the index finger (e.g., ventral aspect of the proximal phalanx of the index finger).

    Data is measured in degrees celsius (point at which cold or warm is detected)

  12. Change in thermal detection thresholds as assessed in Quantitative Sensory testing- warm and cold detection threshold; thermal sensory limen

    Time frame: From baseline to post-intervention (after 6-weeks)

    Thermal detection thresholds will be assessed using a thermode over the index finger (e.g., ventral aspect of the proximal phalanx of the index finger).

    Data is measured in degrees celsius (point at which cold or warm is detected)

  13. Thermal pain thresholds as assessed in Quantitative Sensory testing- warm and cold painful threshold

    Time frame: Baseline

    Pain thermal thresholds will be assessed using a thermode over the index finger (e.g., ventral aspect of the proximal phalanx of the index finger) and over the contralateral lower limb (tibial anterior).

    Data is measured in degrees celsius (point at which cold or warm is initially detected as painful)

  14. Change in thermal pain thresholds as assessed in Quantitative Sensory testing- warm and cold painful threshold

    Time frame: From baseline to post-intervention (after 6-weeks)

    Pain thermal thresholds will be assessed using a thermode over the index finger (e.g., ventral aspect of the proximal phalanx of the index finger) and over the contralateral lower limb (tibial anterior).

    Data is measured in degrees celsius (point at which cold or warm is initially detected as painful)

  15. Mechanical detection thresholds as assessed in Quantitative sensory testing

    Time frame: Baseline

    Mechanical detection thresholds will be assessed using a standardised set of von Frey filaments (mN) over the index finger. Geometric mean will be calculated

  16. Change in mechanical detection thresholds as assessed in Quantitative sensory testing

    Time frame: From baseline to post-intervention (after 6-weeks)

    Mechanical detection thresholds will be assessed using a standardised set of von Frey filaments (mN) over the index finger. Geometric mean wil be calculated

  17. Mechanical pain thresholds as assessed in Quantitative sensory testing

    Time frame: Baseline

    Mechanical pain thresholds will be assessed using a series of weighted pin prick stimulators (mN). They will be assessed over the index finger and over the contralateral lower limb (tibial anterior).

  18. Change in mechanical pain thresholds as assessed in Quantitative sensory testing

    Time frame: From baseline to post-intervention (after 6-weeks)

    Mechanical pain thresholds will be assessed using a series of weighted pin prick stimulators (mN). They will be assessed over the index finger and over the contralateral lower limb (tibial anterior).

  19. Mechanical pain sensitivity as assessed in Quantitative sensory testing

    Time frame: Baseline

    Mechanical pain sensitivity will be assessed using a series of weighted pin prick stimulators (mN) over the index finger. Pain rating for each stimulus on a 0-100 numerical rating scale ('0' indicating "no pain", and '100' indicating "most intense pain imaginable"). Geometric mean of all numerical ratings for pinprick stimuli will be calculated

  20. Change in mechanical pain sensitivity as assessed in Quantitative sensory testing

    Time frame: From baseline to post-intervention (after 6-weeks)

    Mechanical pain sensitivity will be assessed using a series of weighted pin prick stimulators (mN) over the index finger. Pain rating for each stimulus on a 0-100 numerical rating scale ('0' indicating "no pain", and '100' indicating "most intense pain imaginable"). Geometric mean of all numerical ratings for pinprick stimuli will be calculated

  21. Dynamic mechanical allodynia as assessed in Quantitative sensory testing

    Time frame: Baseline

    Pain rating for each stimulus on a 0-100 numerical rating scale ('0' indicating "no pain", and '100' indicating "most intense pain imaginable"). Geometric mean (compound measure) of all numerical ratings across light touch stimulators over the index finger

  22. Change in dynamic mechanical allodynia as assessed in Quantitative sensory testing

    Time frame: From baseline to post-intervention (after 6-weeks)

    Pain rating for each stimulus on a 0-100 numerical rating scale ('0' indicating "no pain", and '100' indicating "most intense pain imaginable"). Geometric mean (compound measure) of all numerical ratings across light touch stimulators over the index finger

  23. Wind-up ratio as assessed in Quantitative sensory testing

    Time frame: Baseline

    Wind-up ration will be assessed using a pin prick (mN) over the index finger (e.g., ventral aspect of the proximal phalanx of the index finger). Ratio, continous data

  24. Change in wind-up ratio as assessed in Quantitative sensory testing

    Time frame: From baseline to post-intervention (after 6-weeks)

    Change in wind-up ration will be assessed using a pin prick (mN) over the index finger (e.g., ventral aspect of the proximal phalanx of the index finger). Ratio, continuous data

  25. Vibration detection thresholds as assessed in Quantitative sensory testing

    Time frame: Baseline

    Vibration detection thresholds will be assessed using a tuning fork (64 Hz, 8/8 scale) over a bony prominence over (e.g., palmar side of the distal end of the second metacarpal)

  26. Change in vibration detection thresholds as assessed in Quantitative sensory testing

    Time frame: From baseline to post-intervention (after 6-weeks)

    Change in vibration detection thresholds will be assessed using a tuning fork (64 Hz, 8/8 scale) over a bony prominence over (e.g., palmar side of the distal end of the second metacarpal)

  27. Pressure pain thresholds as assessed in Quantitative sensory testing

    Time frame: Baseline

    Pressure pain thresholds will be assessed using an algometer (kg) on the thenar eminence and over the contralateral lower limb (tibialis anterior)

  28. Change in pressure pain thresholds as assessed in Quantitative sensory testing

    Time frame: From baseline to post-intervention (after 6-weeks)

    Change in pressure pain thresholds will be assessed using an algometer (kg) on the thenar eminence and over the contralateral lower limb (tibialis anterior)

  29. Pinch strength test - maximum isometric strength

    Time frame: Baseline

    Pinch grip dynamometry. Continuous data, kg

  30. Change in pinch strength test - maximum isometric strength

    Time frame: From baseline to post-intervention (after 6-weeks)

    Pinch grip dynamometry. Continuous data, kg

  31. Nerve mechanosensitivity- upper limb neurodynamic test (median nerve)

    Time frame: Baseline

    Evaluation of nerve mechanosensitivity in response to mechanical load (increased tension) applied to the nerve. Range of elbow extension at point of symptoms (degrees)

  32. Change in nerve mechanosensitivity- upper limb neurodynamic test (median nerve)

    Time frame: From baseline to post-intervention (after 6-weeks)

    Change in nerve mechanosensitivity in response to mechanical load (increased tension) applied to the nerve. Range of elbow extension at point of symptoms (degrees)

  33. Nerve mechanosensitivity - positive upper limb neurodynamic tests

    Time frame: Baseline

    Upper limb neurodynamic tests will be assessed to determine the presence of increased mechanosensitivity. The neurodynamic test will be graded as 'positive', when there is at least partial reproduction of symptoms plus when symptoms can be modified with structural differentiation. Otherwise, the neurodynamic test will be graded as 'negative'

  34. Change in nerve mechanosensitivity - positive upper limb neurodynamic tests

    Time frame: From baseline to post-intervention (after 6-weeks)

    Upper limb neurodynamic tests will be assessed to determine the presence of increased mechanosensitivity. The neurodynamic test will be graded as 'positive', when there is at least partial reproduction of symptoms and when symptoms can be modified with structural differentiation. Otherwise, the neurodynamic test will be graded as 'negative'

  35. Symptom severity and limitations in hand function as assessed by the Boston carpal tunnel syndrome questionnaire

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Patient reported symptoms and limitations on the Boston carpal tunnel syndrome questionnaire

  36. Symptom intensity levels on a Visual Analogue Scale (VAS)

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Patient reported average intensity of pain, paraesthesia and numbness on 10cm visual analogue scales, ranging from no symptoms to worst symptoms ever

  37. Location of symptoms in a body and a hand diagram

    Time frame: Baseline, post-intervention (after 6 weeks)

    Patient reported location of symptoms in a body diagram and a hand diagram.

  38. Presence of central sensitisation as assessed with the Central Sensitisation Inventory

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Patient reported central sensitisation on the Central Sensitisation Inventory

  39. Functional deficits- Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Participant reported outcomes on ability to perform activities as per quick DASH questionnaire

  40. Functional deficits- Patient specific functional scale (PSFS)

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Participant reported outcomes on the patient specific functional scale

  41. Presence of neuropathic pain - DN4

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Patient screened for neuropathic pain using DN4

  42. Presence of neuropathic pain - pain DETECT

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Patient screened for neuropathic pain using pain DETECT

  43. Neuropathic pain symptoms - Neuropathic Pain Symptom Inventory

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Patient reported outcomes on neuropathic pain symptoms as assessed on Neuropathic Pain Symptom Inventory.

  44. Presence of psychological co-morbidities - The Depression, Anxiety, and Positive Outlook Scale (DAPOS)

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Participant reported outcomes on depression and anxiety as per DAPOS

  45. Presence of psychological co-morbidities - short-form Pain Anxiety Symptoms Scale (PASS-20)

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Participant reported outcomes on depression and anxiety as per short-form Pain Anxiety Symptoms Scale (PASS-20)

  46. Presence of psychological co-morbidities - pain catastrophizing scale (PCS)

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Participant reported outcomes on depression and anxiety as per pain catastrophising scale (PCS)

  47. Assessment of quality of life - EQ-5D-5L

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Participant reported outcomes on quality of life as per EQ-5D-5L questionnaire

  48. Assessment of sleep interference - Insomnia Severity Index

    Time frame: Baseline, post-intervention (after 6 weeks), 6-months follow up

    Participant reported outcomes on sleep interference with the Insomnia Severity Index.

  49. Adverse and serious adverse events

    Time frame: From start of intervention until end of intervention (6 weeks)

    Patient self-reported adverse events

  50. Exercise adherence to the neurodynamic home-based intervention - number of sessions

    Time frame: From start of intervention until end of intervention (6 weeks)

    Patient self-reported number of sessions per day throughout the intervention in an exercise diary

Other outcomes

  1. Blood samples - DNA

    Time frame: Baseline

    Blood samples coupled with detailed phenotype data will investigate potential gene associations in CTS and recovery

  2. Change in blood samples - DNA

    Time frame: From baseline to post-intervention (after 6-weeks)

    Change in blood samples coupled with detailed phenotype data will investigate potential gene associations in CTS and recovery

  3. Concentration of serum inflammatory markers - metabolomics

    Time frame: Baseline

    Concentrations of inflammatory markers in serum

  4. Change in the concentration of serum inflammatory markers - metabolomics

    Time frame: From baseline to post-intervention (after 6-weeks)

    Change in the concentrations of inflammatory markers in serum

  5. Pro-inflammatory cytokine levels

    Time frame: Baseline

    Proinflammatory cytokine assay (pg/ml); continuous data

  6. Change in pro-inflammatory cytokine levels

    Time frame: From baseline to post-intervention (after 6-weeks)

    Change in proinflammatory cytokine assay (pg/ml); continuous data

  7. Concentration of inflammatory markers in serial skin biopsies

    Time frame: Baseline

    Concentration of inflammatory markers in skin biopsies. Baseline biopsy will be performed in the most distal part of the ventrolateral side of the proximal phalanx of the index finger. The 6-weeks biopsy will be performed proximally, avoiding the primary biopsy site

  8. Change in concentration of inflammatory markers in serial skin biopsies

    Time frame: From baseline to post-intervention (after 6-weeks)

    Change in concentration of inflammatory markers in skin biopsies. Baseline biopsy will be performed in the most distal part of the ventrolateral side of the proximal phalanx of the index finger. The 6-weeks biopsy will be performed proximally, avoiding the primary biopsy site

Sponsors and collaborators

Lead sponsor

University of Oxford

Other

Collaborators

  • Wellcome Trust

Registry information

Official study title

Mechanisms of Neurodynamic Treatments (MONET)

Acronym: MONET

Important dates

Study start
2023
Primary completion
2025
Study completion
2026
First posted
May 16, 2023
Registry last updated
Jun 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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