Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will test the hypothesis that human brown adipose tissue (BAT) can be activated
      using a β3-adrenergic receptor (AR) agonist. The efficacy of β3-AR agonist will be compared
      with cold exposure, which we have already shown can activate human BAT, as well as a placebo
      control.
    

Detailed description: 
      This study will include an outpatient screening visit and three separate, independent
      overnight study visits in the General Clinical Research Center (GCRC) at Beth Israel
      Deaconess Medical Center (BIDMC). Screening procedures will consist of a medical history,
      physical examination, blood draw, and ECG. If, from the screening tests, it is determined
      that the eligibility criteria have been meet, healthy volunteers will participate in three
      separate inpatient visits at BIDMC. Study procedures will occur in the GCRC and the Nuclear
      Medicine suite at BIDMC.

      Volunteers will first complete Day A, in which we will measure BAT volume and activity during
      cold exposure. Cold exposure will consist of wearing a cooling vest at 55 - 61°F, a
      temperature shown to be cool enough to activate brown adipose tissue but warm enough not to
      lead to shivering. Resting metabolic rate (RMR) will be measured by indirect calorimetry
      before and during cool exposure.

      If there is detectable brown fat activity on Day A, volunteers will participate in Days B and
      C. Days B and C will be conducted in random order to reduce any bias from the sequence of
      treatment and scans, as well as any potential placebo effects. Day B will consist of
      pharmacological stimulation with β3-AR agonist. On Day C, volunteers will be given a placebo
      control and will not undergo cooling.

      A blood draw of 26 cc will always be done prior to FDG injection and FDG PET/CT will always
      be performed 60 minutes after FDG injection. On Day A, FDG will be injected after 60 minutes
      of cool exposure and the volunteer will remain in the cooling vest for another 60 minutes
      after FDG injection.

      To compare energy expenditure and BAT mass and activity among volunteers, we will normalize
      the data to fat and muscle mass. Whole-body and regional fat and muscle mass will be measured
      via a Dual Energy X-ray Absorptiometry (DXA) scan at the end of Day A.
    

Intervention name(s): beta3-adrenergic receptor agonist
Intervention type(s): Drug
Intervention description(s): single dose. The subjects were randomized to receive placebo on one study day and active beta3-adrenergic receptor agonist on the other study day.
Other intervention name(s): mirabegron, which is Myrbetriq (TM) by Astellas Pharma
Intervention MeSH terms: Mirabegron; Adrenergic Agents; Adrenergic Agonists
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: adipose tissue, brown; obesity; Adrenergic beta-3 Receptor Agonists; thermogenesis; metabolism