- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03664934
Pathophysiological Mechanism Behind Prolonged Whiplash Associated Disorders
Study Overview
Detailed Description
BACKGROUND There is no consensus regarding the injury mechanism in complex prolonged Whiplash Associated Disorders (WAD) cases. Often, tissue damage and physiological alterations is not detectable. In order to improve future rehabilitation, a greater understanding of the mechanisms underlying whiplash injury and their importance for treatment success is required. It is also important to investigate if pathophysiological changes can be restored by rehabilitation.
AIM The projects aims to investigate neck muscle structure and function, biomarkers and the association with pain, disability and other outcomes before and after neck-specific exercises.
METHODS Design These are sub-group trials, each one independent of the others, in a prospective, multicentre, randomized controlled trial (RCT) with two parallel treatment arms conducted according to a protocol established before recruitment started (ClinicalTrials.gov Protocol ID: NCT03022812). Physiotherapist-led neck-specific exercise previously shown to be effective for the current population constitutes the control treatment for the new Internet-based neck-specific exercise treatment. In the RCT, a total of 140 patients will be included (70 from each group), whereof 30 (both randomization arms equally) consecutively will be asked to participate in the present sub-group study. The sub-group studies aims to start September 2019. Independent physiotherapists in primary health care will distribute the treatment.
In sub-group of individuals, additional measurements will be performed before and after interventions end (3 months follow-up). The physical measurements will be performed by independent specially trained test-leaders blinded to randomization.
Additionally, 30 neck healthy individuals without serious diseases matched for age and gender will consecutively be investigated.
Study population
The inclusion criteria for patients are:
- Chronic neck problems corresponding to WAD grades 2-3 verified by clinical examination
- Average estimated pain in the last week at least 20 mm on the visual analogue scale (VAS)
- Neck disability of more than 20% on the Neck Disability Index (NDI) [10]
- Working age (18 - 63 years)
- Daily access to a computer/tablet/smart phone and Internet
- Neck symptoms within the first week after the injury (i.e., neck pain, neck stiffness, or cervical radiculopathy).
For the present sub group study additional criteria were:
- Right handed
- Dominant right sided or equal sided pain
Inclusion criteria for healthy controls:
• Age and gender matched healthy individuals without neck pain and disability (VAS <10mm, NDI <5%) that feel overall healthy without known diseases.
Exclusion criteria for patients:
- Individuals with any of the following signs of head injury at the time of whiplash injury will be excluded: loss of consciousness, amnesia before or after the injury, altered mental status (e.g., confusion, disorientation), focal neurological changes (changes in smell and taste).
- Previous fractures or dislocation of the cervical spine
- Known or suspected serious physical pathology included myelopathy,
- Spinal tumours
- Spinal infection
- Ongoing malignancy
- Previous severe neck problems that resulted in sick leave for more than a month in the year before the current whiplash injury
- surgery in the cervical spine
- Generalized or more dominant pain elsewhere in the body
- Other illness/injury that may prevent full participation
- Inability to understand and write in Swedish
Additional criteria in the present sub group:
- Increased risk of bleeding,
- BMI >35
- Contraindications of MRI such as metal, severe obesity, pacemaker and pregnancy.
Exclusion criteria for healthy controls:
- Earlier neck injury,
- Recurrent neck pain,
- Earlier treatment for neck pain.
- Increased risk of bleeding,
- BMI >35
- Contraindications of MRI
Recruitment and randomization Information about the study will be provided by healthcare providers, reports in newspapers, social media, and the university's website. Interested patients will contact the research team through the project website. After completing a small survey on the website, a project team member (physiotherapist) will perform a telephone interview and ask about the patient's medical history. An appointment for a physical examination and additional interview for the present sub-group study is made as a last step to ensure that the criteria for study participation are met. If the study criteria are met, written and oral informed consent are obtained, and the patient will fill out a questionnaire and undergo physical measurements of neck-related function. Baseline measurements must be completed for inclusion.
Healthy individuals will consecutively be recruited among friends, family and staff at the university or the university hospital to suit the age and gender of a patient.
Intervention for the patient group The intervention consists of neck-specific exercises distributed in two different ways, twice a week at the physiotherapist clinic for 3 months (NSE group) or with 4 physiotherapy visits only combined with a web-based system (NSEIT group).
A. In the NSE group, patients will get an explanation and justification for the exercise consisting of basic information about the musculoskeletal anatomy of the neck relevant to the exercises given by the physiotherapist in order to motivate the patient and help make them feel safe and reassured. The patients undergo a 12-week training programme with a physiotherapist 2 days/week (total 24 times). Exercises are chosen from a clear and written frame of exercises. The training includes exercises for the deep neck muscles, continuing with the endurance training of neck and shoulder muscles. The exercises are individually adjusted according to the individual's physical conditions and progressively increased in severity and dose. Exercise-related pain provocation is not accepted. The patient may also perform exercises at home. At the end of the treatment period, the participants are encouraged to continue practising on their own. The exercises have been used with good results in previous RCTs.
B. In the NSEIT group, patients will receive the same information and training programmes as the NSE group, but with 4 visits to the physiotherapist instead of 24. Exercises are introduced, progressed, and followed up to ensure correct performance. The exercises are performed and most of the information is given with the help of Internet support outside the healthcare system. Photos and videos of the exercises (a clear stepwise progression) and information are available on the Web-based system. A SMS reminder is automatically available if the exercise diary is not completed. The time required for training is the same as in group A, but without the patient having to go to the physiotherapy clinic. The Internet programme was developed by experienced physiotherapists/ researchers together with technicians and clinicians. Technicians are available to assist the participants if any technical difficulties arise. The patients will be introduced to the exercises and get information and support at the physiotherapy visits.
Variables and measurements Background data and data in the RCT include personal details, questionnaires and test results regarding pain, physical and psychological functioning, health and cost-effectiveness described elsewhere (ClinicalTrials.gov Protocol ID: NCT03022812).
Measurements will be done at baseline for both groups and at 3 months follow-up for the patient when treatment ends. Except for blood and saliva samples that will be collected twice (baseline and repeated after 3 months), the measurements will be performed at baseline only for the healthy individuals.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Östergötland
-
Linköping, Östergötland, Sweden, 58183
- Linköping University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Study population
The inclusion criteria for patients are:
- Chronic neck problems corresponding to WAD grades 2-3 verified by clinical examination
- Average estimated pain in the last week at least 20 mm on the visual analogue scale (VAS)
- Neck disability of more than 20% on the Neck Disability Index (NDI) [10]
- Working age (18 - 63 years)
- Daily access to a computer/tablet/smart phone and Internet
- Neck symptoms within the first week after the injury (i.e., neck pain, neck stiffness, or cervical radiculopathy).
For the present sub group study additional criteria were:
- Right handed
- Dominant right sided or equal sided pain
Inclusion criteria for healthy controls:
• Age and gender matched healthy individuals without neck pain and disability (VAS <10mm, NDI <5%) that feel overall healthy without known diseases.
Exclusion criteria for patients:
- Individuals with any of the following signs of head injury at the time of whiplash injury will be excluded: loss of consciousness, amnesia before or after the injury, altered mental status (e.g., confusion, disorientation), focal neurological changes (changes in smell and taste).
- Previous fractures or dislocation of the cervical spine
- Known or suspected serious physical pathology included myelopathy,
- Spinal tumours
- Spinal infection
- Ongoing malignancy
- Previous severe neck problems that resulted in sick leave for more than a month in the year before the current whiplash injury
- surgery in the cervical spine
- Generalized or more dominant pain elsewhere in the body
- Other illness/injury that may prevent full participation
- Inability to understand and write in Swedish
Additional criteria in the present sub group:
- Increased risk of bleeding,
- BMI >35
- Contraindications of MRI such as metal, severe obesity, pacemaker and pregnancy.
Exclusion criteria for healthy controls:
- Earlier neck injury,
- Recurrent neck pain,
- Earlier treatment for neck pain.
- Increased risk of bleeding,
- BMI >35
- Contraindications of MRI such as metal, severe obesity, pacemaker and pregnancy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patients, Neck-specific exercises
Patients before and after neck-specific exercises, subgroup to NCT01528579 with additional measures
|
Neck-specific exercises for chronic whiplash associated disorders
Other Names:
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No Intervention: Healthy controls
Healthy controls, no treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Speckle tracking analyses of neck and shoulder muscle function
Time Frame: Baseline and at 3 months follow-up when intervention ended. The outcome measure is going to report a change over time for patients.
|
Measured with medical ultrasonography during neck and arm exercises
|
Baseline and at 3 months follow-up when intervention ended. The outcome measure is going to report a change over time for patients.
|
Cross-sectional area, volume, fatty infiltration and inflammation of neck muscles
Time Frame: Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Neck and some whole body imaging measured with 3.0 T MRI scanner
|
Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Brain function in cortical networks related to pain
Time Frame: Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Measured with a resting-state fMRI protocol with an echo planar imaging (EPI) sequence
|
Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Biomarkers for inflammation and stress
Time Frame: Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Measured with blood samples and saliva
|
Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Cervikal kinaesthesia
Time Frame: Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Neck-eye coordination
|
Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Balance test
Time Frame: Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Postural sway during single and double leg stance
|
Baseline, 3 months. The outcome measure is going to report a change over time for patients.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neck Disability Index (NDI)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Self-reported neck-specific function.
Score 0 to 50 (or in percentages 0% to 100%); 0p/0%=no disability, 50p/100%=complete activity limitation
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Whiplash Disability Questionnaire
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Disability associated with whiplash, in patients.
Score 0 to 130; 0=no disability, 130=maximum disability.
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Patient-specific functional scale (PSFS)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Individual ratings of function to quantify activity limitations, in patients.
Score 0-10 score; 0= Unable to perform activity, 10= Able to perform activity at the same level as before injury or problem.
Total score=sum of the activity scores/ number of activities.
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Pain intensity in neck, head, and arm and dizziness by a Visual Analogue Scale (VAS) (0-100 mm; where 0=no pain, 100= worst imaginable pain )
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Pain intensity.
Score 0 to 100 mm; 0=no pain, 100=worst imaginable pain
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Distribution of pain by a pain drawing assessed with images
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Distribution of pain, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Frequency of pain
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Frequency of pain, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Use of pain medications
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Use of pain medications, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Dizziness/balance by the Dizziness Handicap Inventory (DHI)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Dizziness questionnaire, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Headache Questions by VAS and the Headache Impact Test (HIT-6)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Impact of headache, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Pain Catastrophizing Scale (PCS), total scores range from 0 - 52; 0=no catastrophizing, 52= maximum catastrophizing
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Self-reported pain catastrophizing, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
EuroQuol five dimensions
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Self-reported health, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Effort Reward Imbalance questionnaire
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Work related balance between effort and reward, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Symptoms Satisfaction scale
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Satisfaction with present symptoms, in patients.
1 to 7 scale; 1=delighted, 7=terrible.
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Physical activity score, a combination score of the 2 questions (everyday physical activity and exercise/sport/open-air activity) to a combined 4-point score
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Physical activity.
Score 0 to 4; 0=inactivity, 4=high activity.
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Health care consumption, number of visits
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Health care consumption, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Self-Efficacy Scale (SES)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Self-reported self-efficacy, in patients.
Score 0-200; 0=no self-efficacy, 200=strong self-efficacy
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Fear Avoidance Beliefs Questionnaire (FABQ)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Fear Avoidance Beliefs, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Hospital Anxiety and Depression Scale (HAD)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Depression and anxiety.
Each subscale (depression and anxiety) range from 0 to 21; 0=normal, 21=severe
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Post Traumatic Stress Disorder checklist (PCL-S)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Post Traumatic Stress, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Range of neck motion
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Range of motion, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Ergonomics questions and how work is perceived
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Work ergonomics, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Sickness presence by the Stanford presenteeism scale (SPS-6)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Sickness presence at work, impact of health problems on individual work performance and overall perceived productivity , in patients.
Scores 6-30, with lower scores indicting lower Presenteeism, and higher scores indicating higher Presenteeism.
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Patient Enablement Instrument (PEI) questionnaire
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Patient enablement, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Consumption of analgesic drugs prescribed through the drug registry
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Consumption of analgesic drugs, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Sick-leave registration, number of days and episodes
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Sick-leave, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Cognitive failures questionnaire (CFQ)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Cognitive function, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Sensorimotor control of the neck muscles, mm Hg
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Sensorimotor control, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Neck muscle endurance of ventral and dorsal neck muscles in seconds
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Neck muscle endurance, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Balance measured in seconds, standing on one leg with eyes closed
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Balance, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Neurology
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Clinical examination of neurology, in patients, such as reflexes, sensibility, muscle weakness, Spurling´s test, neural tension test.
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Work Ability Index (WAI)
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Self-reported work ability, in patients
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Global rating of change scale
Time Frame: Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Overall change because of the treatment, in patients.
Score -5 (very much worse to +5 completely recovered and importance of change 0=not at all important, 100= very important.
|
Change from baseline to 3 months (the end of treatment) and 15 months (1 year after study treatment is finalized) follow-up
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Background data such as age and gender, living circumstances
Time Frame: Baseline
|
Background data such as age, gender, living circumstances
|
Baseline
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Anneli Peolsson, Professor, Linkoeping University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Linköping University
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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