Neurohormonal Benefits of Exercise in Fibromyalgia and PTSD
Condition: FM and PTSD
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Study type: Interventional

Summary: 
      The most recent conflicts are creating a new generation of Veterans, including an increasing
      number of women Veterans, who present with comorbid PTSD and chronic pain conditions,
      including Fibromyalgia (FM), from deployment-related physical injuries and exposure to
      psychological trauma. Health behavior change is important in treating these conditions and
      proactively preventing long-term negative health sequelae, in order to benefit these Veterans
      directly and reduce the challenges to our healthcare system. The proposed SPiRE application
      will use an innovative translational research approach to study whether a progressive -based
      exercise program will reduce FM pain in patients with PTSD and to elucidate and modify
      potential PTSD-related deficiencies in neurobiological and psychological responses to
      exercise to optimize the physical and psychological benefits of exercise for these
      individuals.
    

Detailed description: 
      Due to the COVID-19 pandemic, and after consultation with the appropriate research oversight,
      this study is temporarily suspended as of 3/15/20.

      This study will compare the effects of a 12-week progressive exercise training program on 1)
      Fibromyalgia (FM) pain and PTSD symptoms, 2) pain threshold and tolerance, and 3) relevant
      biomarkers and neuromodulators including: a) anti-stress, anti-nociceptive, immune modulating
      factors such as neuropeptide Y (NPY) and GABAergic neuroactive steroids such as
      allopregnanolone and pregnanolone (together termed ALLO) b) factors that upregulate the
      expression of NPY and the GABAergic neuroactive steroids, and otherwise modulate
      inflammation, such as cortisol, c) excitatory factors such as substance P that directly
      promote pain transduction and d) pro-inflammatory cytokines such as IL-6 and IL-8 that not
      only increase pain and inflammation, but also contribute to psychological dysfunction (e.g.
      anhedonia and depression) via impact on the CNS reward system. This study will focus on
      Veterans with FM/PTSD. The study design includes a baseline, acute, cardiopulmonary exercise
      assessment (CPX) that will inform the exercise prescription for a 12-week "progressive
      exercise" training program, comprised of three 30-45 minute exercise sessions per week
      (walking or running, depending on the ability/capacity of the participant). Exercise sessions
      will be initially supervised by an exercise physiologist in the Clinical Studies Unit (CSU)
      at the VA Boston Healthcare System and then each participant will transition into the home.
      Weekly telephone calls by the PI will provide additional motivational support and problem
      solving. Implementation of the prescribed exercise regimen will also be supported by the use
      of heart rate and actigraph monitors programmed for the participant to achieve their
      prescribed heart rate range (HRR). Finally, an "endpoint" CPX assessment will occur at week
      13 to track changes in psychological and neurobiological factors and to delineate their
      impact on pain and PTSD symptoms. Both CPX, maximum load, exercise tests will be performed in
      accordance with guidelines published by the American College of Cardiology. Among Veterans
      with FM/PTSD, changes in the biomarkers assessed after acute, CPX exercise testing will be
      associated with improvements in pain and PTSD symptoms.

      Once identified, such biomarkers could be augmented by modification of the exercise regimen
      to help enhance the anti-stress hormone levels for the FM/PTSD population and experience
      clinically significant reductions in their symptoms. To obtain sufficient power, 36
      participants (18/year) will be recruited. Data from this pilot work will be used to
      demonstrate feasibility and inform the further development of individually prescribed
      exercise regimens and a motivationally based exercise behavior change intervention aimed at
      reducing chronic musculoskeletal pain, including FM, and PTSD symptoms in Veterans. In the
      short-term, this SPiRE proposal will allow the PI to develop a more effective, motivationally
      based, exercise behavior change protocol that fosters long-term exercise adherence in
      patients with FM/PTSD. In the long-term, this intervention will be used as an adjunct to
      cognitive interventions for these disorders to be further developed and studied via a larger
      VA, NIH, or DOD-funded grant for which the PI will apply year 2 of the current SPiRE
      proposal.
    

Intervention name(s): Progressive Exercise Training
Intervention type(s): Behavioral
Intervention description(s): Designed to ease primarily sedentary individuals into exercise training, increasing in intensity up to 80% of maximum Heart Rate Range over time.
Intervention model: Single Group Assignment
Intervention model description: Using an innovative translational research approach to study whether a 12 week-progressive - exercise program will reduce FM pain in patients with PTSD and to elucidate and modify potential PTSD-related deficiencies in neurobiological and psychological responses to exercise
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Fibromyalgia and PTSD