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

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

Background issues and controversies
More than ever before, there is a rise in the rates of obesity and diabetes. As opposed to white fat which stores excess calories, brown fat – also known as brown adipose tissue or BAT-consumes this energy to generate heat. In settings of increased food consumption and cold-exposure, studies show that human BAT becomes more active, potentially combatting weight gain. Other emerging evidence indicates that human BAT may be an endocrine organ, releasing hormones into the blood and regulating other organs like skeletal muscle, liver, and the insulin-releasing pancreatic beta-cell. However, alongside these promising studies are those people who believe that there is not enough BAT in humans to be functionally relevant, and it contributes little to heat generation or overall health.
Purpose/Rationale of the proposed study
One of the principal reasons for skepticism about the ability to utilize human BAT is that there is not very much compared to smaller animals in which BAT activation has shown such promise. Therefore, a critical step is to develop medicines that can grow BAT in people and evaluate what kind of health benefits can be achieved.
Specific objectives
This study will administer the clinically-available beta3-AR agonist, mirabegron (Myrbetriq , Astellas Pharma). We will determine whether we can increase BAT volume and activity in people after they have taken this medication daily for four weeks. Our current goal is to see if chronic administration of mirabegron leads to an increase in BAT volume and metabolic activity and if it produces health benefits.
Key elements of what is involved
At the beginning of the study, the participants will undergo a series of tests to determine their baseline amounts of BAT, blood sugar status, and levels of specified hormones. The testing will take place over the course of two to three days while an inpatient on the Metabolic Patient Care Unit at the NIH Clinical Center. Depending on the Cohort, participants will then take the medication alone for four weeks or both the medication and placebo for four weeks each, during which time they will continue their standard daily routines. At two weeks after starting placebo or mirabegron, participants will return for one day for the assessment of any interim changes and to validate safety. At the end of each set of four weeks there will be a second set of inpatient testing over two to three days. Participants will be brought back two weeks after finishing the study for a follow-up safety visit, at which time they will receive an ECG and heart rate monitoring.
Primary outcomes
The primary outcome is either the change in BAT metabolic activity as measured by 18FFDG PET/CT or glucose infusion rate as measured by a hyperinsulinemic euglycemic clamp. Secondary endpoints will examine multiple other factors, including body weight, fat mass, glucose tolerance, changes in levels of hormones, and improved liver function.

Source: View full study details on ClinicalTrials.gov

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December 13, 2022Comments OffClinicalTrials.gov | Endocrinology Clinical Trials | Endocrinology Studies | US National Library of Medicine
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