Clinical trial NCT04940923: Neuroinflammation as a Predictor of Chronicity in Whiplash
Official title: Does Peripheral Neuroinflammation Predict Chronicity Following Whiplash?
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Whiplash Injuries
Keywords: Magnetic resonance imaging
Pain threshold
Neuritis
Prognosis
Lead sponsor: University of Sussex
Sponsor class: OTHER
Collaborators: name: University of Oxford
First posted: 2021-06-28
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: People who have sustained a whiplash injury less than 4 weeks prior to their participation in the study.

Healthy volunteers.

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.


Eligibility criteria: 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

Primary outcomes:
measure: MRI T2-weighted nerve signal strength
timeFrame: Baseline
measure: Change in MRI T2-weighted nerve signal strength
timeFrame: From baseline to 6 months
measure: Fractional anisotropy from diffusion tensor images
timeFrame: Baseline
measure: Change in fractional anisotropy from Diffusion tensor images
timeFrame: From baseline to 6 months
Secondary outcomes:
measure: T1 MRI median nerve morphology
timeFrame: Baseline
measure: Changes to T1 MRI median nerve morphology
timeFrame: From baseline to 6 months
measure: Pro-inflammatory cytokine levels
timeFrame: Baseline
measure: Change in Pro-inflammatory cytokine levels
timeFrame: From baseline to 6 months
measure: Tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)
timeFrame: Baseline
measure: Change to tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)
timeFrame: From baseline to 6 months
measure: Tests for heightened nerve mechanosensitivity- Pressure pain threshold
timeFrame: Baseline
measure: Change in heightened nerve mechanosensitivity- Pressure pain threshold
timeFrame: From baseline to 6 months
measure: Quantitative sensory testing- warm and cold pain thresholds
timeFrame: Baseline
measure: Change to Quantitative sensory testing- warm and cold pain thresholds
timeFrame: From baseline to 6 months
measure: Quantitative sensory testing- Mechanical pain threshold
timeFrame: Baseline
measure: Change in Quantitative sensory testing- Mechanical pain threshold
timeFrame: From baseline to 6 months
measure: Quantitative sensory testing- Pressure pain threshold
timeFrame: Baseline
measure: Change in quantitative sensory testing- Pressure pain threshold
timeFrame: From baseline to 6 months
measure: Changes in Pain levels on Visual analogue scale
timeFrame: From baseline to 6 months
measure: Change in Neck disability index
timeFrame: From baseline to 6 months
measure: Change in painDETECT questionnaire
timeFrame: From baseline to 6 months
measure: Change in Short post-traumatic stress inventory
timeFrame: From baseline to 6 months
Other outcomes:
Locations:
city: Brighton
country: United Kingdom
facility: Brighton and Sussex Medical School
state: East Sussex
city: Oxford
country: United Kingdom
facility: Oxford Neuroscience, University of Oxford
state: Oxfordshire
Study officials:
affiliation: Brighton and Sussex Medical School
name: Andrew Dilley, PhD
role: PRINCIPAL_INVESTIGATOR
References: