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Clinical Trial Summary

One emerging, highly modifiable homeostatic mechanism for energy expenditure in humans is brown adipose tissue (BAT) thermogenesis. BAT is currently considered a prime target for the treatment of obesity and Type 2 diabetes (T2D). Using acetate and fluorodeoxyglucose (FDG) positron emission tomography (PET) , It has been demonstrated that BAT thermogenesis is inducible by chronic cold exposure. BAT activation through cold exposure is associated with improved glucose homeostasis and insulin sensitivity. A pharmaceutical approach, which seemed to be very promising to stimulate the activation of BAT, was the use of a selective beta 3-adrenergic receptor agonist, mirabegron. Nevertheless, in a later study, It has been demonstrated that human BAT thermogenesis is under the control of beta-2, not beta-3, adrenergic receptor. The most selective beta-2 adrenergic receptor agonist approved for clinical use in Canada is formoterol fumarate, given in inhalation for the treatment of asthma (Oxeze®). In summary, BAT contributes to cold-induced thermogenesis and is recruited by chronic cold exposure as well as by a growing number of food supplements and drugs. Intracellular triglyceride (TG) is the primary source of fuel for BAT thermogenesis under normal physiological conditions, as blocking intracellular TG lipolysis using nicotinic acid abolishes BAT thermogenesis. Beta-2 adrenergic stimulation is the pharmacological target to activate BAT thermogenesis in humans and may also lead to white adipose tissue lipolysis. Using a highly-selective beta-2 receptor agonist with and without administration of nicotinic acid would thus give the opportunity to quantify more precisely energy expenditure accounted by BAT thermogenesis and white adipose tissue metabolism in humans.


Clinical Trial Description

Each participant will undergo three metabolic sessions with PET imaging using [11C]-palmitate, [11C]-acetate and [18F]-FDG: 1. during a 3-h cold exposure (Study A, control condition) 2. after inhalation of Formoterol with oral nicotinic acid (Study B) 3. after inhalation of Formoterol only (Study C). ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05553184
Study type Interventional
Source Université de Sherbrooke
Contact
Status Completed
Phase N/A
Start date July 5, 2022
Completion date May 29, 2023

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