Whiplash InjuriesNCT04940923
Neuroinflammation as a Predictor of Chronicity in Whiplash
An observational study of Whiplash Injuries, run by University of Sussex at 2 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Whiplash Injuries
- What is being tested?
- MRI
- How many people
- 147 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 1 Jun 2021to Apr 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: People who have sustained a whiplash injury less than 4 weeks prior to their participation in the study. Healthy volunteers.
Who may be able to join
- 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:
Show all 10Show fewer
- 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
Who cannot join
- 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):
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites, 2 recruiting
- Recruiting
Brighton and Sussex Medical School
Brighton, East Sussex, BN1 9RY
Colette Ridehalgh, PhD, +441273075260, c.ridehalgh@bsms.ac.uk
Andrew Dilley, PhD, +441273 877094, A.Dilley@BSMS.ac.uk
- Recruiting
Oxford Neuroscience, University of Oxford
Oxford, Oxfordshire, OX3 9DU
Annina Schmid, PhD, +44 1865 223254, annina.schmid@ndcn.ox.ac.uk
Joel Fundaun, joel.fundaun@ndcn.ox.ac.uk
About this study
Official title: Does Peripheral Neuroinflammation Predict Chronicity Following Whiplash?
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
- Being tested
- MRI
- Keywords
- Magnetic resonance imaging, Pain threshold, Neuritis, Prognosis
- Medical subject headings
- Whiplash Injuries, Neuritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIDiagnostic test
Also called Quantitative sensory tests, Blood serum tests, Clinical tests, Questionnaires
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
| Study group | Role | What they receive |
|---|---|---|
| Patients | Patients within 4 weeks of a whiplash injury. Receives: Diagnostic Test: MRI | |
| Healthy controls | Age and gender matched healthy controls Receives: Diagnostic Test: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI T2-weighted nerve signal strength
T2-weighted nerve signal strength in the brachial plexus and median nerve compared to healthy control group
Measured: 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
Measured: From baseline to 6 months
Fractional anisotropy from diffusion tensor images
Fractional anisotropy measurements from brachial plexus and median nerve compared to healthy controls
Measured: Baseline
Change in fractional anisotropy from Diffusion tensor images
Fractional anisotropy from brachial plexus and median nerve compared to baseline
Measured: From baseline to 6 months
Secondary outcomes (18)
T1 MRI median nerve morphology
ratio/mm2; continuous data
Measured: Baseline
Changes to T1 MRI median nerve morphology
ratio/mm2; continuous data
Measured: From baseline to 6 months
Pro-inflammatory cytokine levels
Proinflammatory cytokine assay (pg/ml) continuous data
Measured: Baseline
Change in Pro-inflammatory cytokine levels
Proinflammatory cytokine assay (pg/ml) continuous data
Measured: From baseline to 6 months
Tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)
Measures heightened response to tensile load applied to the nerve. Range of elbow extension at point of symptoms (degrees)
Measured: Baseline
Change to tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)
Measures heightened response to tensile load applied to the nerve. Range of elbow extension at point of symptoms (degrees)
Measured: From baseline to 6 months
Tests for heightened nerve mechanosensitivity- Pressure pain threshold
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.
Measured: Baseline
Change in heightened nerve mechanosensitivity- Pressure pain threshold
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.
Measured: From baseline to 6 months
Quantitative sensory testing- warm and cold pain thresholds
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)
Measured: Baseline
Change to Quantitative sensory testing- warm and cold pain thresholds
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)
Measured: From baseline to 6 months
Quantitative sensory testing- Mechanical pain threshold
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
Measured: Baseline
Change in Quantitative sensory testing- Mechanical pain threshold
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
Measured: From baseline to 6 months
Quantitative sensory testing- Pressure pain threshold
Thresholds measured over thenar eminance using an algometer (Kg). Pressure applied and participant indicates when pressure changes to pain (mean of 3)
Measured: Baseline
Change in quantitative sensory testing- Pressure pain threshold
Thresholds measured over thenar eminance using an algometer (Kg). Pressure applied and participant indicates when pressure changes to pain (mean of 3)
Measured: From baseline to 6 months
Changes in Pain levels on Visual analogue scale
Participant indicated pain level on a 10cm scale of 0-10
Measured: From baseline to 6 months
Change in Neck disability index
Neck disability index. Scale -10 questions each scored 0-5. Total score /50
Measured: From baseline to 6 months
Change in painDETECT questionnaire
A measure of neuropathic pain. A continuous scale: 0-38 or trichotomised: no, unclear, yes. A score of >19 suggests neuropathic pain.
Measured: From baseline to 6 months
Change in Short post-traumatic stress inventory
A measure of post traumatic stress - 8 questions scale of 0-3
Measured: From baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2021
- Study start1 Jun 2021
- Primary completionMar 2023 (estimated)
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Whiplash InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 147 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sussex
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford
- Responsible party
- Sponsor
- Investigators
- Andrew Dilley, PhD, Principal investigator, Brighton and Sussex Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04940923
- Sponsor's protocol ID
- 278291/ 070 DIL
- Status last verified
- Nov 2022
- First submitted
- 9 Jun 2021
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 41081757Ridehalgh 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.
PubMed 40035629Ridehalgh 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.
PubMed 36521884
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Peripheral Neuroinflammation Predict Chronicity Following Whiplash?
- ClinicalTrials.gov ID
- NCT04940923
- Acronym / sponsor ID
- 278291/ 070 DIL
- Conditions
- Whiplash Injuries
- Keywords
- Magnetic resonance imaging, Pain threshold, Neuritis, Prognosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 147 participants (estimated)
- Lead sponsor
- University of SussexUniversity, hospital or other
- Collaborators
- University of Oxford
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- Mar 2023 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 28 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Diagnostic Test: MRIPatients within 4 weeks of a whiplash injury. |
| Healthy controls | – | Diagnostic Test: MRIAge and gender matched healthy controls |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- People who have sustained a whiplash injury less than 4 weeks prior to their participation in the study. Healthy volunteers.
Key inclusion criteria (10 listed)
- 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
- Free of neck or upper limb pain
Key exclusion criteria (11 listed)
- 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
- Unsuitability to undergo MRI (assessed with the MRI screening questionnaire)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIAlso: Quantitative sensory tests, Blood serum tests, Clinical tests, QuestionnairesT2 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 | Diagnostic test | Healthy controls, Patients |
Primary outcome
MRI T2-weighted nerve signal strength
Time frame: 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
Time frame: 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
Fractional anisotropy from diffusion tensor images
Time frame: Baseline
Fractional anisotropy measurements from brachial plexus and median nerve compared to healthy controls
Change in fractional anisotropy from Diffusion tensor images
Time frame: From baseline to 6 months
Fractional anisotropy from brachial plexus and median nerve compared to baseline
18 secondary outcomes
T1 MRI median nerve morphology
Time frame: Baseline
Changes to T1 MRI median nerve morphology
Time frame: From baseline to 6 months
Pro-inflammatory cytokine levels
Time frame: Baseline
Change in Pro-inflammatory cytokine levels
Time frame: From baseline to 6 months
Tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)
Time frame: Baseline
Change to tests for heightened nerve mechanosensitivity- upper limb neurodynamic test (median nerve)
Time frame: From baseline to 6 months
Tests for heightened nerve mechanosensitivity- Pressure pain threshold
Time frame: Baseline
Change in heightened nerve mechanosensitivity- Pressure pain threshold
Time frame: From baseline to 6 months
Quantitative sensory testing- warm and cold pain thresholds
Time frame: Baseline
Change to Quantitative sensory testing- warm and cold pain thresholds
Time frame: From baseline to 6 months
Quantitative sensory testing- Mechanical pain threshold
Time frame: Baseline
Change in Quantitative sensory testing- Mechanical pain threshold
Time frame: From baseline to 6 months
Quantitative sensory testing- Pressure pain threshold
Time frame: Baseline
Change in quantitative sensory testing- Pressure pain threshold
Time frame: From baseline to 6 months
Changes in Pain levels on Visual analogue scale
Time frame: From baseline to 6 months
Change in Neck disability index
Time frame: From baseline to 6 months
Change in painDETECT questionnaire
Time frame: From baseline to 6 months
Change in Short post-traumatic stress inventory
Time frame: From baseline to 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Derived from this study: PubMed 41081757Ridehalgh 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.
- Derived from this study: PubMed 40035629Ridehalgh 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.
- Derived from this study: PubMed 36521884Ridehalgh 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Dilley, PhD principal investigator
Brighton and Sussex Medical School
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Whiplash Injuries, run by University of Sussex at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrew Dilley, PhD (+44 1273 877094, a.dilley@bsms.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRI T2-weighted nerve signal strength (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04940923, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.