Clinical trial NCT03949959: Effectiveness of Physiotherapy Following PRP for Chronic Whiplash
Official title: Effectiveness of Conservative Multimodal Physiotherapy in Chronic Whiplash-associated Disorders With Facet-mediated Pain Undergoing Platelet Rich Plasma (PRP) Treatment: a Series of Single Case Experimental Designs (SCEDs).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Whiplash Injuries
Neck Injuries
Platelet Rich Plasma
Keywords: Physiotherapy
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2019-05-14
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A Single Case Experimental Design (SCED) will be used to evaluate the intervention. Participants act as their own controls, and thus are exposed to both the treatment and control conditions. The study will be conducted and reported according to the Singe Case Reporting guidelines in BEhavioural Interventions (SCRIBE). A randomised, concurrent, multiple-baseline A1 (baseline control) - B (intervention)-A2 (follow-up withdrawal) design will be used to meet the methodological recommendations for SCEDs. Participants will be randomly allocated to a 5, 8 or 11 day baseline period during which they will undertake their usual activities. The baseline phase will be followed by a 6-week intervention period during which participants will participate in 10, one hour sessions with an experienced post-graduate trained physiotherapist. The intervention phase will be followed by a 12-week follow-up phase where participants will have no contact with the intervention personnel.
Primary purpose: TREATMENT

Brief summary: The investigators will explore a standardized and previously published evidence-based conservative multimodal physiotherapy treatment fulfilling clinical practice guidelines in individuals with chronic whiplash-associated disorders (WAD) with facet-mediated pain (appropriate response to dual medial branch blocks) undergoing cervical facet joint Plasma-Rich Platelet (PRPt) and compare health outcomes to individuals' undergoing cervical facet joint PRP with usual care (PRPu), which consists of advice, supervised home exercise and pharmacological management for treatment of residual pain. To be clear, the investigators are not investigating the efficacy or effectiveness of cervical facet joint PRP - these individuals have already consented to proceed with PRP treatment. The investigators are evaluating the role of adjuvant conservative multimodal physiotherapy treatment. It must be noted that these patients have previously failed to respond to conservative physiotherapy. The investigators will use a design which is quite novel in physiotherapy, Single Case Experimental Designs (SCEDs). In contrast to an experimental group design in which one group is compared with another, participants in single-subject research provide their own control data for the purpose of comparison in a within-subject rather than a between-subjects design. SCEDs provide a method to determine response and benefit for every individual patient.

Therefore, the investigators will assess effectiveness of conservative multimodal physiotherapy for chronic WAD with facet-mediated pain undergoing cervical facet joint PRP, using patients as their own control, in a multiple baseline design.

Detailed description: This will be a single case with randomized multiple baseline experimental design with enrolment of 3 patients undergoing PRPt, and 3 patients undergoing PRPu following PRP. There will be a variable length baseline (A1) and then a staggered start to provide internal validity - one patient starting at 5 days (post-PRP), one at 8 (post-PRP) and one at 11 days post-PRP, randomly allocated. This study will utilise an A1-B-A2 design: a baseline (A1 no intervention); intervention phase (B); and a no intervention (A2 follow up).

Primary outcome measures will be collected daily during this time period. The baseline phase will be followed by a 6-week intervention period (B). Participants will have 10 one hour sessions over a 6-week period. The intervention will be delivered by an experienced physiotherapist with postgraduate qualifications. During the intervention period, once or twice per week the daily collection of the primary outcome measures will coincide with the delivery of each intervention session. The intervention phase will be followed by a 12-week follow-up phase (A2) where participants will have no contact with the intervention personnel. This follow-up phase is implemented in order to determine the possible duration of improvement post intervention. All outcome measures will be collected at the completion of this 12-week follow-up period.

Secondary outcome measures for generalisation purposes will be collected prior to commencing PRP, at the end of the intervention period (which coincides with the commencement of the no-intervention period), and at the end of the no-intervention period; totalling 3 sampling points throughout the study duration.

Eligibility criteria: Inclusion Criteria:

* Individuals with Grade II Whiplash Associated Disorder with \> 80% relief of familiar neck pain after dual medial branch blocks
* \> 12 weeks since injury and failed to respond to previous (\> 6 weeks) conservative treatment
* Neck pain on numerical pain rating scale ≥ 4/10
* Neck Disability Index \> 28%

Exclusion Criteria:

* Presence of dizziness symptoms
* Known or suspected serious spinal pathology (e.g. metastatic disease of the spine);
* Confirmed fracture or dislocation at time of injury (i.e., WAD Grade IV)
* Nerve root compromise (i.e., WAD Grade III)
* Spinal surgery in the past 12 months; and
* History of any mental health conditions such as bipolar disorder, psychosis, schizophrenia, anxiety, PTSD or severe depression
* Inability to stop taking anti-inflammatory medications for 3-days prior to, or 10-days following PRP
* Unable to understand +/- complete validated questionnaire items in English

Primary outcomes:
measure: Pain, Enjoyment of Life and General Activity (PEG)
timeFrame: 12 weeks
measure: Self-efficacy whilst performing daily activities in chronic WAD.
timeFrame: 12 weeks
Secondary outcomes:
measure: Neck Disability Index (NDI)
timeFrame: Up to 11 days + 12 weeks
measure: Patient Global Impression of Change (-3 to +3 scale)
timeFrame: Up to 11 days + 12 weeks
measure: Depression & Anxiety Stress Scales (DASS-21)
timeFrame: Up to 11 days + 12 weeks
measure: The Pain Catastrophizing Scale (PCS)
timeFrame: Up to 11 days + 12 weeks
measure: Medical Outcomes Survey Short Form (SF-12)
timeFrame: Up to 11 days + 12 weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Vivo Cura Health
state: Alberta
Study officials:
affiliation: University of Calgary
name: Ashley Smith, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carroll LJ, Holm LW, Hogg-Johnson S, Cote P, Cassidy JD, Haldeman S, Nordin M, Hurwitz EL, Carragee EJ, van der Velde G, Peloso PM, Guzman J; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Course and prognostic factors for neck pain in whiplash-associated disorders (WAD): results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine (Phila Pa 1976). 2008 Feb 15;33(4 Suppl):S83-92. doi: 10.1097/BRS.0b013e3181643eb8.
citation: Curatolo M, Bogduk N, Ivancic PC, McLean SA, Siegmund GP, Winkelstein BA. The role of tissue damage in whiplash-associated disorders: discussion paper 1. Spine (Phila Pa 1976). 2011 Dec 1;36(25 Suppl):S309-15. doi: 10.1097/BRS.0b013e318238842a.
citation: Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective outcome measures. J Manipulative Physiol Ther. 2004 Jan;27(1):26-35. doi: 10.1016/j.jmpt.2003.11.003.
citation: Jull G, Sterling M, Kenardy J, Beller E. Does the presence of sensory hypersensitivity influence outcomes of physical rehabilitation for chronic whiplash?--A preliminary RCT. Pain. 2007 May;129(1-2):28-34. doi: 10.1016/j.pain.2006.09.030. Epub 2007 Jan 10.
citation: Kaneoka K, Ono K, Inami S, Hayashi K. Motion analysis of cervical vertebrae during whiplash loading. Spine (Phila Pa 1976). 1999 Apr 15;24(8):763-9; discussion 770. doi: 10.1097/00007632-199904150-00006.
citation: Krebs EE, Lorenz KA, Bair MJ, Damush TM, Wu J, Sutherland JM, Asch SM, Kroenke K. Development and initial validation of the PEG, a three-item scale assessing pain intensity and interference. J Gen Intern Med. 2009 Jun;24(6):733-8. doi: 10.1007/s11606-009-0981-1. Epub 2009 May 6.
citation: Lamb SE, Gates S, Williams MA, Williamson EM, Mt-Isa S, Withers EJ, Castelnuovo E, Smith J, Ashby D, Cooke MW, Petrou S, Underwood MR; Managing Injuries of the Neck Trial (MINT) Study Team. Emergency department treatments and physiotherapy for acute whiplash: a pragmatic, two-step, randomised controlled trial. Lancet. 2013 Feb 16;381(9866):546-56. doi: 10.1016/S0140-6736(12)61304-X. Epub 2012 Dec 19.
citation: Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: the ultimate strategy for individualizing medicine? Per Med. 2011 Mar;8(2):161-173. doi: 10.2217/pme.11.7.
citation: Lord SM, Barnsley L, Wallis BJ, Bogduk N. Chronic cervical zygapophysial joint pain after whiplash. A placebo-controlled prevalence study. Spine (Phila Pa 1976). 1996 Aug 1;21(15):1737-44; discussion 1744-5. doi: 10.1097/00007632-199608010-00005.
citation: Lord SM, Barnsley L, Wallis BJ, McDonald GJ, Bogduk N. Percutaneous radio-frequency neurotomy for chronic cervical zygapophyseal-joint pain. N Engl J Med. 1996 Dec 5;335(23):1721-6. doi: 10.1056/NEJM199612053352302.
citation: McDonald GJ, Lord SM, Bogduk N. Long-term follow-up of patients treated with cervical radiofrequency neurotomy for chronic neck pain. Neurosurgery. 1999 Jul;45(1):61-7; discussion 67-8. doi: 10.1097/00006123-199907000-00015.
citation: Michaleff ZA, Maher CG, Lin CW, Rebbeck T, Jull G, Latimer J, Connelly L, Sterling M. Comprehensive physiotherapy exercise programme or advice for chronic whiplash (PROMISE): a pragmatic randomised controlled trial. Lancet. 2014 Jul 12;384(9938):133-41. doi: 10.1016/S0140-6736(14)60457-8. Epub 2014 Apr 4.
citation: Nguyen RT, Borg-Stein J, McInnis K. Applications of platelet-rich plasma in musculoskeletal and sports medicine: an evidence-based approach. PM R. 2011 Mar;3(3):226-50. doi: 10.1016/j.pmrj.2010.11.007.
citation: Quinn KP, Winkelstein BA. Detection of altered collagen fiber alignment in the cervical facet capsule after whiplash-like joint retraction. Ann Biomed Eng. 2011 Aug;39(8):2163-73. doi: 10.1007/s10439-011-0316-3. Epub 2011 May 3.
citation: Ritchie C, Hendrikz J, Jull G, Elliott J, Sterling M. External validation of a clinical prediction rule to predict full recovery and ongoing moderate/severe disability following acute whiplash injury. J Orthop Sports Phys Ther. 2015 Apr;45(4):242-50. doi: 10.2519/jospt.2015.5642.
citation: Ritchie C, Hendrikz J, Kenardy J, Sterling M. Derivation of a clinical prediction rule to identify both chronic moderate/severe disability and full recovery following whiplash injury. Pain. 2013 Oct;154(10):2198-2206. doi: 10.1016/j.pain.2013.07.001. Epub 2013 Jul 4.
citation: Romeiser Logan L, Hickman RR, Harris SR, Heriza CB. Single-subject research design: recommendations for levels of evidence and quality rating. Dev Med Child Neurol. 2008 Feb;50(2):99-103. doi: 10.1111/j.1469-8749.2007.02005.x.
citation: Sampson S, Gerhardt M, Mandelbaum B. Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med. 2008 Dec;1(3-4):165-74. doi: 10.1007/s12178-008-9032-5.
citation: Siegmund GP, Myers BS, Davis MB, Bohnet HF, Winkelstein BA. Mechanical evidence of cervical facet capsule injury during whiplash: a cadaveric study using combined shear, compression, and extension loading. Spine (Phila Pa 1976). 2001 Oct 1;26(19):2095-101. doi: 10.1097/00007632-200110010-00010.
citation: Smith AD, Jull G, Schneider G, Frizzell B, Hooper RA, Dunne-Proctor R, Sterling M. Cervical radiofrequency neurotomy reduces psychological features in individuals with chronic whiplash symptoms. Pain Physician. 2014 May-Jun;17(3):265-74.
citation: Smith AD, Jull G, Schneider GM, Frizzell B, Hooper RA, Sterling M. Modulation of Cervical Facet Joint Nociception and Pain Attenuates Physical and Psychological Features of Chronic Whiplash: A Prospective Study. PM R. 2015 Sep;7(9):913-921. doi: 10.1016/j.pmrj.2015.03.014. Epub 2015 Mar 21.
citation: Smith AD, Jull G, Schneider G, Frizzell B, Hooper RA, Sterling M. A comparison of physical and psychological features of responders and non-responders to cervical facet blocks in chronic whiplash. BMC Musculoskelet Disord. 2013 Nov 4;14:313. doi: 10.1186/1471-2474-14-313.
citation: Smith AD, Jull G, Schneider G, Frizzell B, Hooper RA, Sterling M. Cervical radiofrequency neurotomy reduces central hyperexcitability and improves neck movement in individuals with chronic whiplash. Pain Med. 2014 Jan;15(1):128-41. doi: 10.1111/pme.12262. Epub 2013 Oct 18.
citation: Southerst D, Nordin MC, Cote P, Shearer HM, Varatharajan S, Yu H, Wong JJ, Sutton DA, Randhawa KA, van der Velde GM, Mior SA, Carroll LJ, Jacobs CL, Taylor-Vaisey AL. Is exercise effective for the management of neck pain and associated disorders or whiplash-associated disorders? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. Spine J. 2016 Dec;16(12):1503-1523. doi: 10.1016/j.spinee.2014.02.014. Epub 2014 Feb 15.
citation: Stemper BD, Yoganandan N, Pintar FA. Validation of a head-neck computer model for whiplash simulation. Med Biol Eng Comput. 2004 May;42(3):333-8. doi: 10.1007/BF02344708.
citation: Sterling M. A proposed new classification system for whiplash associated disorders--implications for assessment and management. Man Ther. 2004 May;9(2):60-70. doi: 10.1016/j.math.2004.01.006.
citation: Sterling M. Differential development of sensory hypersensitivity and a measure of spinal cord hyperexcitability following whiplash injury. Pain. 2010 Sep;150(3):501-506. doi: 10.1016/j.pain.2010.06.003. Epub 2010 Jul 1.
citation: Sterling M, Hendrikz J, Kenardy J. Compensation claim lodgement and health outcome developmental trajectories following whiplash injury: A prospective study. Pain. 2010 Jul;150(1):22-28. doi: 10.1016/j.pain.2010.02.013. Epub 2010 Mar 21.
citation: Sterling M, Hendrikz J, Kenardy J. Similar factors predict disability and posttraumatic stress disorder trajectories after whiplash injury. Pain. 2011 Jun;152(6):1272-1278. doi: 10.1016/j.pain.2011.01.056. Epub 2011 Mar 10.
citation: Sterling M, Hendrikz J, Kenardy J, Kristjansson E, Dumas JP, Niere K, Cote J, deSerres S, Rivest K, Jull G. Assessment and validation of prognostic models for poor functional recovery 12 months after whiplash injury: a multicentre inception cohort study. Pain. 2012 Aug;153(8):1727-1734. doi: 10.1016/j.pain.2012.05.004. Epub 2012 Jun 1.
citation: Sterling M, Jull G, Kenardy J. Physical and psychological factors maintain long-term predictive capacity post-whiplash injury. Pain. 2006 May;122(1-2):102-8. doi: 10.1016/j.pain.2006.01.014. Epub 2006 Mar 9.
citation: Sterling M, Jull G, Vicenzino B, Kenardy J, Darnell R. Physical and psychological factors predict outcome following whiplash injury. Pain. 2005 Mar;114(1-2):141-8. doi: 10.1016/j.pain.2004.12.005. Epub 2005 Jan 21.
citation: Stewart MJ, Maher CG, Refshauge KM, Herbert RD, Bogduk N, Nicholas M. Randomized controlled trial of exercise for chronic whiplash-associated disorders. Pain. 2007 Mar;128(1-2):59-68. doi: 10.1016/j.pain.2006.08.030. Epub 2006 Oct 9.
citation: Tate RL, Perdices M, Rosenkoetter U, Shadish W, Vohra S, Barlow DH, Horner R, Kazdin A, Kratochwill T, McDonald S, Sampson M, Shamseer L, Togher L, Albin R, Backman C, Douglas J, Evans JJ, Gast D, Manolov R, Mitchell G, Nickels L, Nikles J, Ownsworth T, Rose M, Schmid CH, Wilson B. The Single-Case Reporting Guideline In BEhavioural Interventions (SCRIBE) 2016 Statement. Neuropsychol Rehabil. 2017 Jan;27(1):1-15. doi: 10.1080/09602011.2016.1190533. Epub 2016 Aug 8.
citation: Teasell RW, McClure JA, Walton D, Pretty J, Salter K, Meyer M, Sequeira K, Death B. A research synthesis of therapeutic interventions for whiplash-associated disorder (WAD): part 2 - interventions for acute WAD. Pain Res Manag. 2010 Sep-Oct;15(5):295-304. doi: 10.1155/2010/640164.
citation: Teasell RW, McClure JA, Walton D, Pretty J, Salter K, Meyer M, Sequeira K, Death B. A research synthesis of therapeutic interventions for whiplash-associated disorder (WAD): part 4 - noninvasive interventions for chronic WAD. Pain Res Manag. 2010 Sep-Oct;15(5):313-22. doi: 10.1155/2010/487279.
citation: Vernon H, Mior S. The Neck Disability Index: a study of reliability and validity. J Manipulative Physiol Ther. 1991 Sep;14(7):409-15.
citation: Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. doi: 10.1097/00005650-199603000-00003.
citation: Winkelstein BA, Santos DG. An intact facet capsular ligament modulates behavioral sensitivity and spinal glial activation produced by cervical facet joint tension. Spine (Phila Pa 1976). 2008 Apr 15;33(8):856-62. doi: 10.1097/BRS.0b013e31816b4710.
citation: Wu J, Zhou J, Liu C, Zhang J, Xiong W, Lv Y, Liu R, Wang R, Du Z, Zhang G, Liu Q. A Prospective Study Comparing Platelet-Rich Plasma and Local Anesthetic (LA)/Corticosteroid in Intra-Articular Injection for the Treatment of Lumbar Facet Joint Syndrome. Pain Pract. 2017 Sep;17(7):914-924. doi: 10.1111/papr.12544. Epub 2017 Feb 22.
citation: Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin Nurs. 2005 Aug;14(7):798-804. doi: 10.1111/j.1365-2702.2005.01121.x.
citation: Lord SM, Barnsley L, Bogduk N. Percutaneous radiofrequency neurotomy in the treatment of cervical zygapophysial joint pain: a caution. Neurosurgery. 1995 Apr;36(4):732-9. doi: 10.1227/00006123-199504000-00014.
citation: Lovibond, S., & Lovibond, P. (1995). Manual for the Depression Anxiety Stress Scales (2nd ed.). Sydney: Psychology Foundation.
citation: Nikles, J. (2015). What are N-of-1 Trials? In J. Nikles & G. Mitchell (Eds.), The Essential Guide to N-of-1 Trials in Health (pp. 9-17). Dordrecht: Springer Netherlands.
citation: Parker, R. I., Vannest, K. J., & Brown, L. (2009). The improvement rate difference for single case research. Exceptional Children, 75, 135-150
citation: Podd D. Platelet-rich plasma therapy: origins and applications investigated. JAAPA. 2012 Jun;25(6):44-9. doi: 10.1097/01720610-201206000-00009. No abstract available.
citation: SIRA - Guidelines for the management of acute whiplash associated disorders - for health professionals. (2014).
citation: Sullivan, M., Bishop, S., & Pivik, J. (1995). The pain catastrophizing scale: development and validation. Psychol Assess, 7, 524-532
citation: Van den Noortgate, W., & Onghena, P. (2007). The aggregation of single-case results using hierarchical linear models. The Behavior Analyst Today, 8(2), 196-209
citation: TRACsa - Clinical guidelines for best practice management of acute and chronic whiplash-associated disorders (2008).
citation: Jull, G., Sterling, M., Falla, D., et al. (2008). Whiplash, Headache and Neck Pain (1 ed.): Churchill Livingstone.