Neuroinflammation as a Predictor of Chronicity in Whiplash

NCT04940923 | Unknown

• 1 other identifier: 278291/ 070 DIL
• Study Type: observational
• Target: 147
• Locations: 1 country
• Sites: 2

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.

Conditions

Whiplash Injuries

Keywords

Magnetic resonance imaging; Pain threshold; Neuritis; Prognosis

Outcome Measures

Primary Outcomes (4)

• MRI T2-weighted nerve signal strength

  T2-weighted nerve signal strength in the brachial plexus and median nerve compared to healthy control group

  Baseline

• Change in MRI T2-weighted nerve signal strength

  Change in T2-weighted nerve signal strength in the brachial plexus and median nerve at 6 months compared to baseline

  From baseline to 6 months

• Fractional anisotropy from diffusion tensor images

  Fractional anisotropy measurements from brachial plexus and median nerve compared to healthy controls

  Baseline

• Change in fractional anisotropy from Diffusion tensor images

  Fractional anisotropy from brachial plexus and median nerve compared to baseline

  From baseline to 6 months

Secondary Outcomes (18)

• T1 MRI median nerve morphology

  Baseline

• Changes to T1 MRI median nerve morphology

  From baseline to 6 months

• Pro-inflammatory cytokine levels

  Baseline

• Change in Pro-inflammatory cytokine levels

  From baseline to 6 months

• Tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)

  Baseline

Study Arms (2)

Patients

Patients within 4 weeks of a whiplash injury.

Diagnostic Test: MRI

Healthy controls

Age and gender matched healthy controls

Diagnostic Test: MRI

Interventions

MRI DIAGNOSTIC_TEST

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

Also known as: Quantitative sensory tests, Blood serum tests, Clinical tests, Questionnaires

Healthy controls; Patients

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• Patients:
• Male and female patients with chronic whiplash associated disorder that meet the Quebec Task Force Classification of whiplash grade II
• Within approximately four weeks of their whiplash injury
• Age 18-60
• Participants capable of giving informed consent
• Healthy Volunteers:
• Free of neck or upper limb pain
• 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.
• Age 18-60
• Participants capable of giving informed consent

You may not qualify if:

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

Sponsors & Collaborators

• University of Sussex: lead
• University of Oxford: collaborator

Study Sites (2)

Brighton and Sussex Medical School

Brighton, East Sussex, BN1 9RY, United Kingdom

RECRUITING

Oxford Neuroscience, University of Oxford

Oxford, Oxfordshire, OX3 9DU, United Kingdom

RECRUITING

Related Publications (3)

• Ridehalgh C, Fundaun J, Bremner S, Cercignani M, Koushesh S, Schmid AB, Dilley A. Temporal development of peripheral neuroinflammation in whiplash-associated disorder grade II and its role in chronicity. Pain. 2026 Feb 1;167(2):356-371. doi: 10.1097/j.pain.0000000000003816. Epub 2025 Oct 10.

  PMID: 41081757 DERIVED

• Ridehalgh C, Fundaun J, Bremner S, Cercignani M, Koushesh S, Young R, Novak A, Greening J, Schmid AB, Dilley A. Evidence for peripheral neuroinflammation after acute whiplash. Pain. 2025 Oct 1;166(10):2285-2299. doi: 10.1097/j.pain.0000000000003560. Epub 2025 Mar 4.

  PMID: 40035629 DERIVED

• Ridehalgh C, Fundaun J, Bremner S, Cercignani M, Young R, Trivedy C, Novak A, Greening J, Schmid A, Dilley A. Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort study. BMJ Open. 2022 Dec 15;12(12):e066021. doi: 10.1136/bmjopen-2022-066021.

  PMID: 36521884 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood and serum

MeSH Terms

Conditions

Whiplash Injuries; Neuritis

Condition Hierarchy (Ancestors)

Neck Injuries; Wounds and Injuries; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Andrew Dilley, PhD

  Brighton and Sussex Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Dilley, PhD

CONTACT

+44 1273 877094; a.dilley@bsms.ac.uk

Colette Ridehalgh, PhD

CONTACT

+44 1273 075260; c.ridehalgh@bsms.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 28, 2021
• Study Start: June 1, 2021
• Primary Completion: March 1, 2023
• Study Completion: April 1, 2024
• Last Updated: November 4, 2022

Record last verified: 2022-11

Locations

GB (2)