Mechanisms of Neurodynamic Treatments
- Conditions
- Diffusion MRIPhysiotherapyCarpal Tunnel SyndromeNeurodynamic TreatmentMechanistic TrialNerve Mobilisation
- Interventions
- Other: AdviceOther: Neurodynamic exercisesDrug: Steroid injection (Depomedrone 40mg)
- Registration Number
- NCT05859412
- Lead Sponsor
- University of Oxford
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 108
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Advice Advice The advice group will receive advice but no additional intervention during the 6 week intervention period (negative control group) Neurodynamic exercises Neurodynamic exercises 6-weeks home exercise programme of nerve and tendon gliding exercises Steroid injection Steroid injection (Depomedrone 40mg) Steroid injection (Depomedrone 40mg) Single steroid injection into Carpal Tunnel (positive control group)
- Primary Outcome Measures
Name Time Method Median nerve fractional anisotropy as determined on diffusion weighted imaging Baseline Fractional anisotropy will be extracted from regions-of-interest in the median nerve and compared to healthy control group
Change in median nerve fractional anisotropy as determined on diffusion weighted imaging 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 Outcome Measures
Name Time Method Change in nerve markers on anatomical MRI From baseline to post-intervention (after 6-weeks) Measured at the median nerve and cervical dorsal root ganglia. ratio/mm2; continuous data
Nerve markers on diffusion weighted imaging: water diffusivity (mm2/s) Baseline Measured at the median nerve and cervical dorsal root ganglia. mm2/s; continuous data
Exercise adherence to the neurodynamic home-based intervention - number of sessions 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
Change in thermal detection thresholds as assessed in Quantitative Sensory testing- warm and cold detection threshold; thermal sensory limen 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)Wind-up ratio as assessed in Quantitative sensory testing 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
Vibration detection thresholds as assessed in Quantitative sensory testing 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)
Change in vibration detection thresholds as assessed in Quantitative sensory testing 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)
Nerve markers on anatomical MRI Baseline Measured at the median nerve and cervical dorsal root ganglia. ratio/mm2; continuous data
Changes in median nerve MRI T2 mapping From baseline to post-intervention (after 6-weeks) ms; continuous data
Thermal pain thresholds as assessed in Quantitative Sensory testing- warm and cold painful threshold 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)Median nerve MRI magnetisation transfer ratio (MTR) Baseline ratio; continuous data
Change to nerve markers on diffusion weighted imaging: water diffusivity (mm2/s) From baseline to post-intervention (after 6-weeks) Measured at the median nerve and cervical dorsal root ganglia. mm2/s; continuous data
Median nerve MRI T2 mapping Baseline ms; continuous data
Changes in median nerve MRI magnetisation transfer ratio (MTR) From baseline to post-intervention (after 6-weeks) ratio; continuous data
Changes in median nerve conduction velocities from electrodiagnostic studies (m/s) From baseline to post-intervention (after 6-weeks) m/s; continuous data
Changes in median sensory nerve action potentials (SNAPs) and compound muscle action potentials (CMAPs): amplitudes (mV) From baseline to post-intervention (after 6-weeks) mV; continuous data
Thermal detection thresholds as assessed in Quantitative Sensory testing - warm and cold detection threshold; thermal sensory limen 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)Mechanical pain thresholds as assessed in Quantitative sensory testing 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).
Change in mechanical pain sensitivity as assessed in Quantitative sensory testing 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
Pinch strength test - maximum isometric strength Baseline Pinch grip dynamometry. Continuous data, kg
Change in nerve mechanosensitivity - positive upper limb neurodynamic tests 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'
Symptom severity and limitations in hand function as assessed by the Boston carpal tunnel syndrome questionnaire Baseline, post-intervention (after 6 weeks), 6-months follow up Patient reported symptoms and limitations on the Boston carpal tunnel syndrome questionnaire
Location of symptoms in a body and a hand diagram Baseline, post-intervention (after 6 weeks) Patient reported location of symptoms in a body diagram and a hand diagram.
Functional deficits- Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire Baseline, post-intervention (after 6 weeks), 6-months follow up Participant reported outcomes on ability to perform activities as per quick DASH questionnaire
Presence of neuropathic pain - pain DETECT Baseline, post-intervention (after 6 weeks), 6-months follow up Patient screened for neuropathic pain using pain DETECT
Presence of psychological co-morbidities - The Depression, Anxiety, and Positive Outlook Scale (DAPOS) Baseline, post-intervention (after 6 weeks), 6-months follow up Participant reported outcomes on depression and anxiety as per DAPOS
Assessment of sleep interference - Insomnia Severity Index Baseline, post-intervention (after 6 weeks), 6-months follow up Participant reported outcomes on sleep interference with the Insomnia Severity Index.
Change in mechanical detection thresholds as assessed in Quantitative sensory testing 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
Change in pressure pain thresholds as assessed in Quantitative sensory testing 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)
Adverse and serious adverse events From start of intervention until end of intervention (6 weeks) Patient self-reported adverse events
Mechanical detection thresholds as assessed in Quantitative sensory testing 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
Change in mechanical pain thresholds as assessed in Quantitative sensory testing 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).
Mechanical pain sensitivity as assessed in Quantitative sensory testing 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
Dynamic mechanical allodynia as assessed in Quantitative sensory testing 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
Change in wind-up ratio as assessed in Quantitative sensory testing 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
Pressure pain thresholds as assessed in Quantitative sensory testing Baseline Pressure pain thresholds will be assessed using an algometer (kg) on the thenar eminence and over the contralateral lower limb (tibialis anterior)
Change in pinch strength test - maximum isometric strength From baseline to post-intervention (after 6-weeks) Pinch grip dynamometry. Continuous data, kg
Neuropathic pain symptoms - Neuropathic Pain Symptom Inventory Baseline, post-intervention (after 6 weeks), 6-months follow up Patient reported outcomes on neuropathic pain symptoms as assessed on Neuropathic Pain Symptom Inventory.
Change in thermal pain thresholds as assessed in Quantitative Sensory testing- warm and cold painful threshold 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)Change in dynamic mechanical allodynia as assessed in Quantitative sensory testing 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
Nerve mechanosensitivity- upper limb neurodynamic test (median nerve) 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)
Change in nerve mechanosensitivity- upper limb neurodynamic test (median nerve) 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)
Nerve mechanosensitivity - positive upper limb neurodynamic tests 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'
Presence of central sensitisation as assessed with the Central Sensitisation Inventory Baseline, post-intervention (after 6 weeks), 6-months follow up Patient reported central sensitisation on the Central Sensitisation Inventory
Functional deficits- Patient specific functional scale (PSFS) Baseline, post-intervention (after 6 weeks), 6-months follow up Participant reported outcomes on the patient specific functional scale
Presence of psychological co-morbidities - pain catastrophizing scale (PCS) Baseline, post-intervention (after 6 weeks), 6-months follow up Participant reported outcomes on depression and anxiety as per pain catastrophising scale (PCS)
Assessment of quality of life - EQ-5D-5L Baseline, post-intervention (after 6 weeks), 6-months follow up Participant reported outcomes on quality of life as per EQ-5D-5L questionnaire
Symptom intensity levels on a Visual Analogue Scale (VAS) 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
Presence of neuropathic pain - DN4 Baseline, post-intervention (after 6 weeks), 6-months follow up Patient screened for neuropathic pain using DN4
Presence of psychological co-morbidities - short-form Pain Anxiety Symptoms Scale (PASS-20) 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)
Trial Locations
- Locations (1)
Nuffield Department of Clinical Neurosciences, University of Oxford
🇬🇧Oxford, Oxfordshire, United Kingdom