Neuroinflammation as a Predictor of Chronicity in Whiplash

Recruiting

• Conditions: Whiplash Injuries
• Interventions: Diagnostic Test: MRI

• Registration Number: NCT04940923
• Lead Sponsor: University of Sussex

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-06-01
• Study First Submitted: 2021-06-09
• Study First Submitted QC: 2021-06-17
• Study First Posted: 2021-06-28
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-03
• Last Update Posted: 2022-11-04
• Primary Completion: 2023-03
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 147

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients	MRI	Patients within 4 weeks of a whiplash injury.
Healthy controls	MRI	Age and gender matched healthy controls

Primary Outcome Measures

Name	Time	Method
Fractional anisotropy from diffusion tensor images	Baseline	Fractional anisotropy measurements from brachial plexus and median nerve compared to healthy controls
Change in fractional anisotropy from Diffusion tensor images	From baseline to 6 months	Fractional anisotropy from brachial plexus and median nerve compared to baseline
MRI T2-weighted nerve signal strength	Baseline	T2-weighted nerve signal strength in the brachial plexus and median nerve compared to healthy control group
Change in MRI T2-weighted nerve signal strength	From baseline to 6 months	Change in T2-weighted nerve signal strength in the brachial plexus and median nerve at 6 months compared to baseline

Secondary Outcome Measures

Name	Time	Method
Change in Quantitative sensory testing- Mechanical pain threshold	From baseline to 6 months	Thresholds 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
Quantitative sensory testing- Pressure pain threshold	Baseline	Thresholds 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 threshold	From baseline to 6 months	Thresholds measured over thenar eminance using an algometer (Kg). Pressure applied and participant indicates when pressure changes to pain (mean of 3)
T1 MRI median nerve morphology	Baseline	ratio/mm2; continuous data
Tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)	Baseline	Measures heightened response to tensile load applied to the nerve. Range of elbow extension at point of symptoms (degrees)
Quantitative sensory testing- Mechanical pain threshold	Baseline	Thresholds 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
Pro-inflammatory cytokine levels	Baseline	Proinflammatory cytokine assay (pg/ml) continuous data
Tests for heightened nerve mechanosensitivity- Pressure pain threshold	Baseline	Algometer 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 to Quantitative sensory testing- warm and cold pain thresholds	From baseline to 6 months	Thresholds measured over index finger using a thermotester- continuous measured in degrees Celsius (point at which the probe changes to warm pain or cold pain)
Change in Short post-traumatic stress inventory	From baseline to 6 months	A measure of post traumatic stress - 8 questions scale of 0-3
Change in Pro-inflammatory cytokine levels	From baseline to 6 months	Proinflammatory cytokine assay (pg/ml) continuous data
Change in heightened nerve mechanosensitivity- Pressure pain threshold	From baseline to 6 months	Algometer 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 thresholds	Baseline	Thresholds 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)
Changes to T1 MRI median nerve morphology	From baseline to 6 months	ratio/mm2; continuous data
Change in painDETECT questionnaire	From baseline to 6 months	A measure of neuropathic pain. A continuous scale: 0-38 or trichotomised: no, unclear, yes. A score of \>19 suggests neuropathic pain.
Change to tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)	From baseline to 6 months	Measures heightened response to tensile load applied to the nerve. Range of elbow extension at point of symptoms (degrees)
Changes in Pain levels on Visual analogue scale	From baseline to 6 months	Participant indicated pain level on a 10cm scale of 0-10
Change in Neck disability index	From baseline to 6 months	Neck disability index. Scale -10 questions each scored 0-5. Total score /50

Trial Locations

Locations (2)

Oxford Neuroscience, University of Oxford; 🇬🇧 Oxford, Oxfordshire, United Kingdom

Brighton and Sussex Medical School; 🇬🇧 Brighton, East Sussex, United Kingdom