Clinical trial NCT05859412: Mechanisms of Neurodynamic Treatments
Official title: Mechanisms of Neurodynamic Treatments (MONET)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Carpal Tunnel Syndrome
Neurodynamic Treatment
Nerve Mobilisation
Diffusion MRI
Physiotherapy
Mechanistic Trial
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Wellcome Trust
First posted: 2023-05-16
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria

Patients:

1. Patients who have a diagnosis of mild to moderate carpal tunnel syndrome based on a clinical assessment and confirmed with nerve conduction studies.
2. Male or Female, aged 18 years or above.
3. Patient is willing and able to give informed consent for participation in the study.

Healthy participants:

1. Male or female aged 18 years or above.
2. Participant is willing and able to give informed consent for participation in the study.
3. No history of hand or arm symptoms
4. No history of neck pain in the past 3 months
5. No systemic medical condition
6. No strong anticoagulant medication or altered coagulation (e.g., hemophilia) preventing skin biopsies
7. Severe anxiety or depression
8. Participants are required to be age- \& sex-matched to patient participants
9. No contraindications for magnetic resonance scanning at 3T
10. Sufficient command of the English language

Exclusion Criteria

Patients:

1. 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)
2. 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.
3. Patients who have a diagnosis of severe carpal tunnel syndrome based on a clinical assessment and confirmed with electrodiagnostic testing
4. Electrodiagnostic testing revealing abnormalities other than CTS
5. Any other upper limb or neck problem for which they have sought treatment in the past 3 months
6. History of significant trauma to the upper limb or neck
7. Diabetes
8. Hypothyroidism
9. Severe anxiety or depression
10. Patient who is pregnant, lactating, or planning pregnancy during the study.
11. Patients on strong anticoagulant medication or altered coagulation preventing skin biopsies.
12. Contraindications for magnetic resonance imaging (assessed with MRI safety screening questionnaire).
13. Contraindications for steroid injections
14. Insufficient command of the English language

Primary outcomes:
measure: Median nerve fractional anisotropy as determined on diffusion weighted imaging
timeFrame: Baseline
measure: Change in median nerve fractional anisotropy as determined on diffusion weighted imaging
timeFrame: From baseline to post-intervention (after 6-weeks)
Secondary outcomes:
measure: Nerve markers on diffusion weighted imaging: water diffusivity (mm2/s)
timeFrame: Baseline
measure: Change to nerve markers on diffusion weighted imaging: water diffusivity (mm2/s)
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Nerve markers on anatomical MRI
timeFrame: Baseline
measure: Change in nerve markers on anatomical MRI
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Median nerve MRI T2 mapping
timeFrame: Baseline
measure: Changes in median nerve MRI T2 mapping
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Median nerve MRI magnetisation transfer ratio (MTR)
timeFrame: Baseline
measure: Changes in median nerve MRI magnetisation transfer ratio (MTR)
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Changes in median nerve conduction velocities from electrodiagnostic studies (m/s)
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Changes in median sensory nerve action potentials (SNAPs) and compound muscle action potentials (CMAPs): amplitudes (mV)
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Thermal detection thresholds as assessed in Quantitative Sensory testing - warm and cold detection threshold; thermal sensory limen
timeFrame: Baseline
measure: Change in thermal detection thresholds as assessed in Quantitative Sensory testing- warm and cold detection threshold; thermal sensory limen
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Thermal pain thresholds as assessed in Quantitative Sensory testing- warm and cold painful threshold
timeFrame: Baseline
measure: Change in thermal pain thresholds as assessed in Quantitative Sensory testing- warm and cold painful threshold
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Mechanical detection thresholds as assessed in Quantitative sensory testing
timeFrame: Baseline
measure: Change in mechanical detection thresholds as assessed in Quantitative sensory testing
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Mechanical pain thresholds as assessed in Quantitative sensory testing
timeFrame: Baseline
measure: Change in mechanical pain thresholds as assessed in Quantitative sensory testing
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Mechanical pain sensitivity as assessed in Quantitative sensory testing
timeFrame: Baseline
measure: Change in mechanical pain sensitivity as assessed in Quantitative sensory testing
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Dynamic mechanical allodynia as assessed in Quantitative sensory testing
timeFrame: Baseline
measure: Change in dynamic mechanical allodynia as assessed in Quantitative sensory testing
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Wind-up ratio as assessed in Quantitative sensory testing
timeFrame: Baseline
measure: Change in wind-up ratio as assessed in Quantitative sensory testing
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Vibration detection thresholds as assessed in Quantitative sensory testing
timeFrame: Baseline
measure: Change in vibration detection thresholds as assessed in Quantitative sensory testing
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Pressure pain thresholds as assessed in Quantitative sensory testing
timeFrame: Baseline
measure: Change in pressure pain thresholds as assessed in Quantitative sensory testing
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Pinch strength test - maximum isometric strength
timeFrame: Baseline
measure: Change in pinch strength test - maximum isometric strength
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Nerve mechanosensitivity- upper limb neurodynamic test (median nerve)
timeFrame: Baseline
measure: Change in nerve mechanosensitivity- upper limb neurodynamic test (median nerve)
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Nerve mechanosensitivity - positive upper limb neurodynamic tests
timeFrame: Baseline
measure: Change in nerve mechanosensitivity - positive upper limb neurodynamic tests
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Symptom severity and limitations in hand function as assessed by the Boston carpal tunnel syndrome questionnaire
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Symptom intensity levels on a Visual Analogue Scale (VAS)
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Location of symptoms in a body and a hand diagram
timeFrame: Baseline, post-intervention (after 6 weeks)
measure: Presence of central sensitisation as assessed with the Central Sensitisation Inventory
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Functional deficits- Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Functional deficits- Patient specific functional scale (PSFS)
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Presence of neuropathic pain - DN4
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Presence of neuropathic pain - pain DETECT
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Neuropathic pain symptoms - Neuropathic Pain Symptom Inventory
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Presence of psychological co-morbidities - The Depression, Anxiety, and Positive Outlook Scale (DAPOS)
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Presence of psychological co-morbidities - short-form Pain Anxiety Symptoms Scale (PASS-20)
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Presence of psychological co-morbidities - pain catastrophizing scale (PCS)
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Assessment of quality of life - EQ-5D-5L
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Assessment of sleep interference - Insomnia Severity Index
timeFrame: Baseline, post-intervention (after 6 weeks), 6-months follow up
measure: Adverse and serious adverse events
timeFrame: From start of intervention until end of intervention (6 weeks)
measure: Exercise adherence to the neurodynamic home-based intervention - number of sessions
timeFrame: From start of intervention until end of intervention (6 weeks)
Other outcomes:
measure: Blood samples - DNA
timeFrame: Baseline
measure: Change in blood samples - DNA
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Concentration of serum inflammatory markers - metabolomics
timeFrame: Baseline
measure: Change in the concentration of serum inflammatory markers - metabolomics
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Pro-inflammatory cytokine levels
timeFrame: Baseline
measure: Change in pro-inflammatory cytokine levels
timeFrame: From baseline to post-intervention (after 6-weeks)
measure: Concentration of inflammatory markers in serial skin biopsies
timeFrame: Baseline
measure: Change in concentration of inflammatory markers in serial skin biopsies
timeFrame: From baseline to post-intervention (after 6-weeks)
Locations:
city: Oxford
country: United Kingdom
facility: Nuffield Department of Clinical Neurosciences, University of Oxford
state: Oxfordshire
Study officials:
affiliation: University of Oxford
name: Eva Sierra-Silvestre, PhD
role: PRINCIPAL_INVESTIGATOR
References: