Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue|
- BAT activity as measured by 18F-FDG PET/CT [ Time Frame: 60 min after FDG administration ] [ Designated as safety issue: No ]difference in BAT activity measured in placebo and active drug arms
- plasma norepinephrine [ Time Frame: 5 minutes before FDG administration ] [ Designated as safety issue: No ]difference in the plasma concentration of norepinephrine measured in the placebo and active drug arms
|Study Start Date:||February 2013|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Other Name: Lactose
Experimental: beta3-adrenergic receptor agonist
Drug: beta3-adrenergic receptor agonist
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01783470
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Aaron M Cypess, MD, PhD||Beth Israel Deaconess Medical Center & Joslin Diabetes Center|