Neurohormonal Benefits of Exercise in Fibromyalgia and PTSD
Neurohormonal Benefits of Exercise in Fibromyalgia and PTSD
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.
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.
Inclusion Criteria:

 -  Only Veteran and civilian participants in whom a physical examination and medical
 history indicate that the participant meets current diagnostic criteria for FM, as
 specified by the American College of Rheumatology, will be eligible for the study.

 -  Eligible participants who agree to a blood draw for measurement of biomarkers, must be
 free of medications and other substances (e.g., illicit drugs and alcohol) that may
 alter results for 2-6 weeks depending on the medication and frequency of use (which
 must be cleared by MD consultants).

 -  If on pain medications with short half-lives, participants must be off of them for 5
 half-lives before testing, generally about 24 hours.

 -  Any FM participant with an ICD-10 chronic pain diagnosis of a musculoskeletal
 etiology, will also be eligible for inclusion in the study as many individuals with FM
 also have such conditions.

 -  Any participant with a confirmed psychiatric diagnosis of PTSD will be included in the
 study. Individuals in the PTSD group must meet diagnostic criteria for current chronic
 PTSD (>3 months) as assessed by the CAPS-5, 1-Month Diagnostic Version.

 Exclusion Criteria:

 -  Participants will be excluded from participation in the study if they have a life
 threatening or acute physical illness (e.g., cancer)

 -  Current schizophreniform illnesses (except for Psychosis NOS due to PTSD-related
 sensory hallucinations)

 -  Untreated bipolar disorder

 -  Or active suicidal or homicidal ideation requiring clinical intervention

 -  Individuals with current or past alcohol and/or substance dependence (less than three
 months from date of screening assessment) will be excluded

 -  Individuals seeking interventional pain treatment, such as surgical interventions or
 other pain clinic interventions, will also be excluded unless they agree to
 participate in the biomarker procedure prior to the start of their pain intervention.

 -  Finally, participants who have a neuropathic origin to their pain will be excluded.