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Neuroinflammation as a Predictor of Chronicity in Whiplash

Does Peripheral Neuroinflammation Predict Chronicity Following Whiplash?

Status
UNKNOWN
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT04940923
Enrollment
147
Registered
2021-06-28
Start date
2021-06-01
Completion date
2024-04-30
Last updated
2022-11-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Whiplash Injuries

Keywords

Magnetic resonance imaging, Pain threshold, Neuritis, Prognosis

Brief summary

Whiplash describes an injury to the neck caused by a rapid movement of the head. It often occurs during a motor vehicle collision, causing considerable pain and distress. Most patients are diagnosed with whiplash associated disorder grade-2 (WAD2). Half of these patients develop chronic pain. Current treatments for patients are ineffective. It is difficult to predict which patients will develop chronic pain, and therefore how to manage these patients. The characteristics of pain felt by many patients with WAD2 suggests that symptoms are caused by an injury to the nerves in the neck and arm. However, on clinical examination there is no indication that these nerves are significantly injured. Work from the investigators' laboratory suggests that nerves may be inflamed. In this study, the contribution of nerve inflammation to symptoms early following whiplash will be established. It will determine whether clinical tests are able to identify those patients with inflamed nerves. It will also determine whether the presence of nerve inflammation can be used to identify patients who develop chronic pain. The study will recruit 115 patients within one month following a whiplash injury and thirty-two healthy volunteers. Participants will undergo a clinical assessment. A blood sample will be taken to look for inflammatory proteins and magnetic resonance imaging will be used to identify nerve inflammation in the neck and wrist. Questionnaires to establish neck disability, pain quality and psychological distress will be completed. MRI findings will be compared to healthy controls. At six-months, patients will be asked to repeat the questionnaires, which will be used to identify those patients who have recovered. Twenty-five recovered and twenty-five non-recovered patients will undergo a repeat MRI and clinical assessment. Although patients on this study will not directly benefit, the findings will help with early diagnosis and could refocus treatment to reduce chronic pain.

Interventions

DIAGNOSTIC_TESTMRI

T2 weighted and DTI MRI images of brachial plexus and wrist. Quantitative sensory tests include warm and cold detection and pain thresholds, paradoxical heat sensation, mechanical detection thresholds, mechanical pain sensation and thresholds, wind up ratios, vibration thresholds and pressure pain thresholds. Clinical tests include standard neurological tests and test for heightened nerve mechanosensitivity. Blood serum to analyse inflammatory proteins. Questionnaires include neck disability index, painDETECT, PTSD8, pain catastrophising scale, eq-5D-5L, DASS 42 and global perceived recovery

Sponsors

University of Oxford
CollaboratorOTHER
University of Sussex
Lead SponsorOTHER

Study design

Observational model
COHORT
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes

Inclusion criteria

Patients: 1. Male and female patients with chronic whiplash associated disorder that meet the Quebec Task Force Classification of whiplash grade II 2. Within approximately four weeks of their whiplash injury 3. Age 18-60 4. Participants capable of giving informed consent Healthy Volunteers: 1. Free of neck or upper limb pain 2. No history of a whiplash injury or of neck or arm pain lasting \>3 months or any recent cervical or upper limb trauma requiring medical treatment. 3. Age 18-60 4. Participants capable of giving informed consent

Exclusion criteria

Patients: 1. Diagnosis of whiplash grade I (neck complaints without physical signs), III (obvious neurological signs) or IV (fracture or dislocation) 2. Experienced concussion or loss of consciousness as a result of the accident 3. Previous history of whiplash 4. Previous history of neck pain or headaches that required treatment All participants (patients and healthy volunteers): 5. Unsuitability to undergo MRI (assessed with the MRI screening questionnaire) 6. Pregnant 7. History of inflammatory disease (e.g. autoimmune diseases, rheumatoid arthritis), neuropathy, diabetes, cancer or non-medically controlled hypertension 8. Current ongoing steroid treatment 9. Participants with an inadequate understanding of English will also be excluded

Design outcomes

Primary

MeasureTime frameDescription
MRI T2-weighted nerve signal strengthBaselineT2-weighted nerve signal strength in the brachial plexus and median nerve compared to healthy control group
Change in MRI T2-weighted nerve signal strengthFrom baseline to 6 monthsChange in T2-weighted nerve signal strength in the brachial plexus and median nerve at 6 months compared to baseline
Fractional anisotropy from diffusion tensor imagesBaselineFractional anisotropy measurements from brachial plexus and median nerve compared to healthy controls
Change in fractional anisotropy from Diffusion tensor imagesFrom baseline to 6 monthsFractional anisotropy from brachial plexus and median nerve compared to baseline

Secondary

MeasureTime frameDescription
Tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)BaselineMeasures heightened response to tensile load applied to the nerve. Range of elbow extension at point of symptoms (degrees)
Change to tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)From baseline to 6 monthsMeasures heightened response to tensile load applied to the nerve. Range of elbow extension at point of symptoms (degrees)
Tests for heightened nerve mechanosensitivity- Pressure pain thresholdBaselineAlgometer applied to ulnar nerve at the cubital tunnel and median nerve at carpal tunnel. Pressure pain threshold (Kg) at point of change from pressure to pain.
Change in heightened nerve mechanosensitivity- Pressure pain thresholdFrom baseline to 6 monthsAlgometer applied to ulnar nerve at the cubital tunnel and median nerve at carpal tunnel. Pressure pain threshold (Kg) at point of change from pressure to pain.
Quantitative sensory testing- warm and cold pain thresholdsBaselineThresholds measured over index finger using a thermotester- continuous data measured in degrees Celsius (point at which the probe changes to warm pain or cold pain)
Change to Quantitative sensory testing- warm and cold pain thresholdsFrom baseline to 6 monthsThresholds measured over index finger using a thermotester- continuous measured in degrees Celsius (point at which the probe changes to warm pain or cold pain)
Quantitative sensory testing- Mechanical pain thresholdBaselineThresholds measured over index finger using a series of weighted pin prick stimulators (mN). Participant scores pain from 0-100 for each stimulus applied. Geometric mean calculated
T1 MRI median nerve morphologyBaselineratio/mm2; continuous data
Quantitative sensory testing- Pressure pain thresholdBaselineThresholds measured over thenar eminance using an algometer (Kg). Pressure applied and participant indicates when pressure changes to pain (mean of 3)
Change in quantitative sensory testing- Pressure pain thresholdFrom baseline to 6 monthsThresholds measured over thenar eminance using an algometer (Kg). Pressure applied and participant indicates when pressure changes to pain (mean of 3)
Changes in Pain levels on Visual analogue scaleFrom baseline to 6 monthsParticipant indicated pain level on a 10cm scale of 0-10
Change in Neck disability indexFrom baseline to 6 monthsNeck disability index. Scale -10 questions each scored 0-5. Total score /50
Change in painDETECT questionnaireFrom baseline to 6 monthsA measure of neuropathic pain. A continuous scale: 0-38 or trichotomised: no, unclear, yes. A score of \>19 suggests neuropathic pain.
Change in Short post-traumatic stress inventoryFrom baseline to 6 monthsA measure of post traumatic stress - 8 questions scale of 0-3
Change in Quantitative sensory testing- Mechanical pain thresholdFrom baseline to 6 monthsThresholds measured over index finger using a series of weighted pin prick stimulators (mN). Participant scores pain from 0-100 for each stimulus applied. Geometric mean calculated
Changes to T1 MRI median nerve morphologyFrom baseline to 6 monthsratio/mm2; continuous data
Pro-inflammatory cytokine levelsBaselineProinflammatory cytokine assay (pg/ml) continuous data
Change in Pro-inflammatory cytokine levelsFrom baseline to 6 monthsProinflammatory cytokine assay (pg/ml) continuous data

Countries

United Kingdom

Contacts

Primary ContactAndrew Dilley, PhD
a.dilley@bsms.ac.uk+44 1273 877094
Backup ContactColette Ridehalgh, PhD
c.ridehalgh@bsms.ac.uk+44 1273 075260

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 10, 2026