Adenosine and A2A Receptors in Human Brown Adipose Tissue

Study Overview
=================
Brief Summary
-----------------
This study investigates the significance of adenosine and A2A receptors in human brown adipose tissue (BAT) in vivo. Using positron emission tomography (PET), perfusion and the density of A2A receptors will be measured in supraclavicular BAT and other tissues in healthy men. The investigators hypothesize, that adenosine can activate BAT, and that adenosine A2A receptor density changes when BAT is activated by cold exposure. Understanding the mechanisms of BAT activation and the role of endocannabinoids in humans is important and beneficial in fighting against the epidemic of obesity and diabetes.

Detailed Description
-----------------
Adenosine is a purine nucleoside released locally in BAT when noradrenaline and ATP are released from sympathetic nerves. Recently it was found that adenosine activates murine and human brown adipocytes, and recruits beiging of white fat via adenosine A2A receptors (A2AR). Furthermore, studies with mice have shown improvements in glucose homeostasis after administration of A2AR agonists. In this study the investigators use the PET radiotracer [15O]-H2O to quantify perfusion of BAT, white adipose tissue (WAT) and muscle in three conditions: room temperature, cold exposure and intravenous infusion of adenosine. Another PET radiotracer [11C]TMSX is used to quantify adenosine A2A receptor density of BAT, WAT and muscle in room temperature and during cold exposure.

Official Title
-----------------
Adenosine and A2a Receptors in Human Brown Adipose Tissue (AdenoBAT)

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Drug: Adenosine
* Other: Cold exposure


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male sex BMI 20 - 28 kg/m2 Age: 18- 40 years Normal OGTT Healthy, no regular medication Exclusion Criteria: BMI < 20 kg/m2 or BMI > 28 kg/m2 Low or high blood pressure Asthma or other obstructive lung disease Sick sinus syndrome, prolonged QT-interval, or any heart disease Any chronic disease that could affect the study outcome, including diabetes Mental disorder or poor compliance Eating disorder or excessive use of alcohol, tobacco smoking or drug use Past dose of radiation Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each subject participates in PET/CT scans in room temperature conditions, during cold exposure and during i.v. infusion of adenosine.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adenosine<br>Perfusion is measured using PET/CT during intravenous infusion (0.14 mg/kg/min) of adenosine. | Drug: Adenosine<br>* Intravenous infusion of adenosine (0.14 mg/kg) is administered for 5 minutes during PET/CT scan.<br>* Other names: Adenocor;|
| No Intervention: Room temperature<br>Perfusion and A2A receptor density is measured using PET/CT in resting room temperature conditions. | |
| Experimental: Cold exposure<br>Perfusion and A2A receptor density is measured using PET/CT during controlled cold exposure. | Other: Cold exposure<br>* Controlled cold exposure is performed before and during PET/CT scan.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BAT perfusion | Perfusion of BAT with [15O]-H2O PET-CT | Effect within 10 minutes | 
| A2A receptor density in BAT | Density of A2A receptors in BAT measured with [11C]-TMSX PET/CT | Effect within 3 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adipose Tissue, Brown