Neuroinflammation as a Predictor of Chronicity in Whiplash

NCT ID: NCT04940923

Last Updated: 2022-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

147 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-06-01

Study Completion Date

2024-04-30

Brief Summary

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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

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Conditions

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Whiplash Injuries

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Patients

Patients within 4 weeks of a whiplash injury.

MRI

Intervention Type 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

Healthy controls

Age and gender matched healthy controls

MRI

Intervention Type 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

Interventions

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MRI

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

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Quantitative sensory tests Blood serum tests Clinical tests Questionnaires

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Oxford

OTHER

Sponsor Role collaborator

University of Sussex

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrew Dilley, PhD

Role: PRINCIPAL_INVESTIGATOR

Brighton and Sussex Medical School

Locations

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Brighton and Sussex Medical School

Brighton, East Sussex, United Kingdom

Site Status RECRUITING

Oxford Neuroscience, University of Oxford

Oxford, Oxfordshire, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Andrew Dilley, PhD

Role: CONTACT

+44 1273 877094

Colette Ridehalgh, PhD

Role: CONTACT

+44 1273 075260

Facility Contacts

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Colette Ridehalgh, PhD

Role: primary

+441273075260

Andrew Dilley, PhD

Role: backup

+441273 877094

Annina Schmid, PhD

Role: primary

+44 1865 223254

Joel Fundaun

Role: backup

References

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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. 2025 Oct 10. doi: 10.1097/j.pain.0000000000003816. Online ahead of print.

Reference Type DERIVED
PMID: 41081757 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40035629 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36521884 (View on PubMed)

Other Identifiers

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278291/ 070 DIL

Identifier Type: -

Identifier Source: org_study_id

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