Pathophysiological Mechanism Behind Prolonged Whiplash Associated Disorders
Condition: Whiplash Injuries
MeSH terms: Whiplash Injuries
Study type: Interventional

Summary: 
      The knowledge of pathophysiological mechanisms behind prolonged Whiplash Associated Disorders
      (WAD) is insufficient and whether changes can be restored by rehabilitation or not is
      unknown. The aim of these studies are to investigate different parameters to further learn
      about pathophysiological mechanisms (neck muscle fatty infiltration, cross-sectional area,
      volume, inflammation and function, brain structure and activity, biomarkers for stress and
      inflammation, cervical kinaesthesia and balance before and after intervention) and the
      association for clinical outcomes in individuals with chronic WAD (n=30) compared with age
      and gender matched healthy individuals (n=30). Measurements will be made at baseline
      (patients and healthy) and at 3 months (patients only, at the end of treatment). However, for
      the blood and saliva samples, they will be re-investigated in the healthy group as well. The
      study results may contribute to the development of improved understanding and diagnostics in
      chronic WAD that may improve future rehabilitation.
    

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.
    

Intervention name(s): Exercises
Intervention type(s): Other
Intervention description(s): Neck-specific exercises for chronic whiplash associated disorders
Other intervention name(s): No treatment, controls only
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Neck pain, Rehabilitation, Muscles, Clinical Trial,; Diagnostics