Orthostatic Intolerance After Bariatric Surgery
Condition: Orthostatic Intolerance
MeSH terms: Orthostatic Intolerance
Study type: Interventional
Phase: Phase 1

Summary: 
      More than 78 million adults in the U.S. are obese. Bariatric surgery is the only modality
      that results in sustained weight loss along with reversal of diabetes mellitus, and a
      decrease in cardiovascular events. Obesity is associated with increased sympathetic nervous
      system (SNS) activity that contributes to blood pressure regulation; sympathetic
      vasoconstrictor activity is maximally activated upon standing and is fundamental for the
      maintenance of orthostatic tolerance. After bariatric surgery, there is a significant and
      sustained reduction in SNS activity at three and six months after the procedure, which is
      related to weight loss. Recently, multiple retrospective studies have reported an orthostatic
      intolerance (OI) syndrome after bariatric surgery characterized by chronic pre-syncopal
      symptoms, syncope and orthostatic hypotension. In the Vanderbilt University Medical Center
      bariatric surgical center, 741 post-bariatric surgery patients reported OI symptoms, 98
      (13.2%) of these patients, progressed to chronic OI and in17 cases, the OI was so disabling
      that patients initiated treatment with pressor agents. More than 50% of OI cases in the
      cohort developed the condition during a weight-stable period. Hence, investigators propose
      the novel hypothesis that after bariatric surgery, the persistent reduction in SNS activity
      contributes to impaired orthostatic tolerance, which is independent of weight loss.
    

Detailed description: 
      Considering that SNS vasoconstrictor activity depends on synaptic norepinephrine
      concentrations, investigators propose a proof-of-concept study to test the hypothesis that
      the norepinephrine transporter (NET) inhibitor, atomoxetine, which increases synaptic
      norepinephrine concentrations, will improve post-bariatric OI. Understanding the changes in
      SNS activity and its contribution to orthostatic tolerance after bariatric surgery is of
      utmost importance to unravel the mechanisms of a novel and unrecognized syndrome,
      post-bariatric OI. In 2014, nearly 200,000 individuals in the US underwent bariatric surgery,
      and the number of bariatric surgery procedures is expected to increase by 22% each year. It
      is projected, therefore, an increase in the incidence of post-bariatric OI.

      Participants with Roux-en-Y gastric bypass (RYGB) and Vertical sleeve gastrectomy (VSG) will
      be studied.

      OI is a chronic and disabling condition; treatment is challenging because current therapies
      have debatable efficacy.

      The proposed application will not only provide central knowledge on the pathophysiology of
      this new syndrome but also will fill an unmet therapeutic need by repurposing NET inhibitors
      for the treatment of OI.
    

Intervention name(s): Atomoxetine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): atomoxetine 0.5 mg/kg/day.; sugar pill
Other intervention name(s): strattera; sugar pill
Intervention MeSH terms: Atomoxetine Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment