The Physiological Responses and Adaptation of Brown Adipose Tissue to Chronic Treatment With Beta3-Adrenergic Receptor Agonists

Description

Study Description:

This study is intended to address questions about human brown adipose tissue (BAT). Specifically, we plan to visualize BAT activity with acute cold exposure during drug naive and drug experienced visits. Thus, we will be studying changes in BAT activity from a chronic dosage of mirabegron.

Objectives:

Cohort 1: To measure changes in BAT metabolic activity in women seen after four weeks of daily treatment with the beta3-AR agonist mirabegron.

Cohort 2: To measure changes in BAT metabolic activity in men seen after four weeks of daily treatment with 200 mg of the beta3-AR agonist mirabegron compared to placebo

Cohort 3: To compare the changes in insulin sensitivity in each woman after four weeks of daily treatment with 100 mg of the beta3-AR agonist mirabegron with the changes in insulin sensitivity in each woman after four weeks of daily treatment with placebo

Primary Endpoints:

Cohort 1: The change in detectable cold exposure induced BAT metabolic activity in women, as visualized by F-FDG PET/CT.

Cohort 2: The change in detectable cold exposure induced BAT metabolic activity, as visualized by 18F-FDG PET/CT

Cohort 3: The change in glucose infusion rate, as measured by the hyperinsulinemic euglycemic clamp, in women after four weeks of daily treatment with 100 mg of the beta3-AR agonist mirabegron with the change in glucose infusion rate after four weeks of daily treatment with placebo

Secondary Endpoints:

1. To identify changes in metabolic health arising from BAT activation and/or prolonged treatment with regular 100 mg (females) or 200mg (men) doses of mirabegron.
2. To determine if there is an interaction between (a) BMI and (b) age with respect to the capacity to increase BAT metabolic activity.
3. To describe the structural and physiological changes in the adipose tissue depots, including cell lineage, size, and inflammation.
4. To assess whether there are improvements in the liver, including reduced stiffness and quantity of hepatic fat.