Treatment and Assessment of Fibromyalgia
Condition: Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Study type: Interventional

Summary: 
      Fibromyalgia is a common disorder affecting approximately 2% of the Canadian population.
      Patients diagnosed with fibromyalgia commonly present with chronic, widespread pain as well
      as fatigue, depression, mood disturbances, and cognitive symptoms. As a result, fibromyalgia
      has a negative impact on the patient's quality of life, and a negative financial impact for
      them, society, and the healthcare system, through lost wages and delayed diagnosis. Therefore
      a more direct and conclusive method of diagnosis is needed.

      Recently, fibromyalgia diagnosis has been based on the modified American College of
      Rheumatology Preliminary Diagnostic Criteria for fibromyalgia. To assist with diagnosis,
      recent evidence shows that compared to healthy people, people with fibromyalgia present with
      differences on functional MRI (fMRI) whole brain scans, as well as differences in a
      functional blood biomarker challenge test, known as fm/a. The fm/a determines the function of
      the immune system in response to a stimulus, and has been used previously to show that people
      with fibromyalgia have a severely blunted immune response.

      Despite the number of treatment options available, interventions for chronic pain remain
      largely ineffective. In light of its demonstrated effectiveness, safety, and ease of use in
      previous studies, radial shockwave therapy (RSWT) has been selected for inclusion in the
      present study. The main objective of this study is to determine the efficacy and effect of
      RSWT compared to placebo on the symptoms frequently reported in association with
      fibromyalgia. In addition, the fm/a and brain activity associated with pain patterns (fMRI)
      may assist in early diagnosis and prediction of treatment success in patients with
      fibromyalgia.
    

Detailed description: 
      At St. Joseph's Care Group (SJCG) rheumatologist and chronic pain physician will determine if
      a client is eligible to participate in the study using the inclusion/exclusion criteria
      (outlined in the attached grant proposal). Physician would then ask if the client would be
      open to discussing their possible involvement in a research study. If so, a member of the
      research team other than physicians will visit with the client at the Chronic Pain Management
      program at SJCG to discuss the project and complete the informed consent process if the
      client would like to participate.

      Following informed consent, the participant would be assigned to one of two groups following
      a restricted randomization procedure. This will be completed using open-source minimization
      software called Qminim. The process of minimization ensures group sizes are equal and
      eliminates potential bias that may be introduced which is important for clinical research of
      small sizes. Group 1 will receive Radial Shockwave Therapy (RSWT) while group 2 will be the
      placebo group. Once participants in the placebo group have completed the study, RSWT will be
      offered, although it will not be included in the data analysis. Participants will be grouped
      for minimization based on sex and age in the following ranges: 18-30, 31-45, 46-60 years. All
      participant information/group assignment will be coded to maintain confidentiality. Group
      assignment will be unknown to the participant until they complete the study (or withdraw from
      the study).

      The following initial assessments will occur prior to receiving the RSWT or placebo: At SJCG:
      participants will undergo quantitative sensory testing for allodynia and hyperalgesia by one
      of the physicians. At Lakehead University School of Kinesiology: participants will have basic
      demographic information such as height, weight and age, measured and recorded on a data
      abstraction form by a member of the research team. The participant will also be asked to
      consider the most painful spot within each of the 3 most painful regions in his/her body.
      Participants will mark on a 100 millimeter VAS scale at the point that corresponds to the
      pain intensity for each region. The amount of pain will be estimated by measuring in
      millimeters the distance from the "no pain" marker to the mark provided by the participant
      for each question. This will be recorded on the data abstraction form. Pressure pain
      threshold will next be measured on the most painful spot within each of the 3 most painful
      regions using a Baseline© Pressure Tolerance Meter (60 lbs). Pressure will be applied
      perpendicular to the tissue in the three most painful regions as indicated by the
      participant. The participant will be asked to report when the pressure applied to the region
      became painful and the amount of pressure shall be recorded in pounds on the data abstraction
      form. A 30 second rest shall be allowed for recovery and the same technique shall be applied
      to the other painful locations. The specific location of the painful region shall be marked
      and documented by a trained member of the research team. Next, participants will be asked to
      complete the Beighton Scoring Screen for hypermobility, Beck's Depression Scale, and Pain
      Catastrophizing Scale questionnaires. All scores will be recorded on the data abstraction
      form. At Lakehead University (NOSM rooms 1002A, C, D E, F or School of Kinesiology SB-1028):
      participants will be scheduled to have a blood sample drawn by a registered phlebotomist.
      Specialized vacutainers will be used to isolate Peripheral Blood Mononuclear Cells (PBMCs)
      which will be later used in cytokine protein analysis. All blood taken will be labeled with a
      participant code to maintain confidentiality, and stored at NOSM.

      At TBRHSC: 15 randomly selected participants from each group will undergo whole brain
      functional MRI (fMRI) imaging by a member of the research team at TBRHSC. The scans will
      include a resting state fMRI, an 8 minute scan during alternating 30 second on, 30 second off
      evoked pressure pain stimulus, a T1 high resolution anatomical image, and a diffusion tensor
      image. Please see the attached grant proposal for details regarding this imaging method.

      Once the initial measures are completed, participants will be scheduled to begin the
      allocated treatment based on group assignment. Group 1 will receive RSWT to the most painful
      spot within each of the 3 most painful regions, while group 2 (placebo) will receive a
      similar treatment but a soft rubber cap will be applied to the applicator, leaving air
      between the transmitter and the cap and the participant's skin. Treatments will be spaced one
      week apart over a 5 week period of time and will occur at Lakehead University's School of
      Kinesiology, room SB-1028.

      Upon completion of the treatments, participants will complete the same
      measures/questionnaires that were performed at the beginning of the study. Also, one vial of
      blood will be taken again and if the participant was in the fMRI group, they will repeat the
      same imaging sessions detailed above.

      At the conclusion of the study, participants will be invited to participate in a focus group
      lead by another research team member during which qualitative feedback regarding the study
      will be discussed. This is a patient-centred approach that will help the investigators engage
      the fibromyalgia community and allow this input to guide future study design.

      It is anticipated that 50 participants will be enrolled in the study. The main analysis will
      be a comparison of the pre- and post-outcomes, meaning that this is a repeated measures study
      design. This design has the advantage of minimizing the effect of inter-subject variability.
      A power analysis was performed a priori and it was determined that this sample size is
      sufficient; minimum detectable differences of 10% and standard deviation of ±15% resulting in
      a power of 0.892.
    

Intervention name(s): Radial Shockwave Therapy; Placebo Comparator: Group 2 - Placebo Group
Intervention type(s): Device; Other
Intervention description(s): 5 treatments in total scheduled weekly; RSWT to the painful areas will be undertaken with 500 shocks (1.5 bar, 15 Hz), then 1000 shocks (2 bar, 8 Hz), and finally 500 shocks (1.5 bar, 15 Hz) to the most painful spot within each of the 3 most painful regions as described by the participant.; 5 treatments in total scheduled weekly; placebo to the painful areas will be undertaken with 2000 shocks to the most painful spot within each of the 3 most painful regions as described by the participant.
Other intervention name(s): Storz D-Actor 100; Storz D-Actor 100
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Shockwave therapy; fMRI; blood biomarkers