Conditions: Obesity
Keywords: adipose tissue, brown obesity Adrenergic beta-3 Receptor Agonists thermogenesis metabolism
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 15
Healthy volunteers: yes

Brief 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.

Arms:
arm 1: single dose. Each subject was randomized to receive placebo at one visit and then the beta3-adrenergic receptor agonist on another study day.

Interventions: intervention 1: beta3-adrenergic receptor agonist
Intervention descriptions: intervention 1: single dose. The subjects were randomized to receive placebo on one study day and active beta3-adrenergic receptor agonist on the other study day.

Protocol document: