Noradrenergic and Stress-Related Etiologies of Chronic Fatigue Syndrome
Condition: Chronic Fatigue Syndrome
MeSH terms: Fatigue Syndrome, Chronic; Syndrome; Fatigue
Study type: Interventional

Summary: 
      The objective of this study is to measure sympathetic nervous system function and stress
      responses in patients with clinically documented and self-reported chronic fatigue that is
      worsened by stress, compared to healthy controls. Baseline norepinephrine (NE) levels and
      stress-induced NE levels in patients who fulfill criteria for Chronic Fatigue Syndrome (CFS)
      and who self-identify with stress induced worsening fatigue, will be compared to data from
      normal individuals pre and post-stress.
    

Detailed description: 
      Symptoms of Chronic Fatigue Syndrome (CFS) are critically important to study as patients
      report that these symptoms are often profoundly debilitating and an impediment to effective
      daily functioning as well as effective vocational and social functioning, while also
      contributing to a significantly increased risk of psychiatric illness and diminished quality
      of life. Previous Phenome-Wide Association (PheWAS) studies revealed a link between a
      norepinephrine transporter (NET) genetic variant and CFS. Based on the potential function of
      the variant and published literature, elevated norepinephrine (NE) levels may underlie at
      least some cluster of fatigue symptoms. Some patients may experience chronic fatigue that is
      due to an excess of circulating NE, and fatigue symptoms are reported by our patient
      population to be commonly exacerbated by stress. This study will test the hypothesis that in
      a subset of people with severely debilitating fatigue of long duration (>6 months) that is
      worsened by stress identified through the Vanderbilt electronic health record phenotyping
      study, have chronic over-release of the hormone NE into the bloodstream/periphery over time
      that results in an overload of NE. This overload of NE causes a compensatory but deleterious
      effect on the brain and nervous system, including sympathetic effects and dysregulated
      physiologic response to stress. Thus, while numerous currently approved therapies that target
      NET inhibit the transporter, a drug with the opposite mechanism of action, a NET activator
      that would decrease circulating NE, may have efficacy in treating underlying pathophysiology
      of chronic fatigue.

      Baseline NE levels and stress-induced NE levels in patients who fulfill criteria for CFS and
      who self-identify with stress induced worsening fatigue, will be compared to data from normal
      individuals pre and post-stress. After all inclusion criteria has been confirmed, an IV will
      be placed for blood collection, a continuous electrocardiographic trace and blood pressure
      cuff will be placed on the subject's arm and finger. Subjects will undergo a posture study,
      autonomic reflex testing, and Stroop stress testing each followed by blood specimen
      collection. An optional blood draw for DNA analysis will occur after patients have been
      provided lunch. Questionnaires will be completed after study procedures and patients have
      been provided lunch. Study blood collection will total up to 28 milliliters (mL): 5 mL for
      cytokines, 20 mL for catecholamines, and optional 3 mL for DNA.
    

Intervention name(s): Posture Study, Autonomic Function Tests, and a Stress Test
Intervention type(s): Other
Intervention description(s): Participants will undergo a Posture Study, Autonomic Function Tests, and a Stress Test. Participants' blood will be drawn to measure markers of sympathetic nervous system function at baseline, in three postural positions, after autonomic tests, and after a stress test.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: CFS; Stress; Norepinephrine Transporter (NET); Norepinephrine (NE); Healthy Controls; Fatigue