Adenosine and A2A Receptors in Human Brown Adipose Tissue (AdenoBAT)

Turku University Hospital (TYKS)

Status: Completed

Conditions: Obesity

Treatments: Drug: Adenosine; Other: Cold exposure

Study type: Interventional

Funder types: Other

Identifiers

NCT03327168

T201/2015

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Male sex
2. BMI 20 - 28 kg/m2
3. Age: 18- 40 years
4. Normal OGTT
5. Healthy, no regular medication

Exclusion criteria

1. BMI < 20 kg/m2 or BMI > 28 kg/m2
2. Low or high blood pressure
3. Asthma or other obstructive lung disease
4. Sick sinus syndrome, prolonged QT-interval, or any heart disease
5. Any chronic disease that could affect the study outcome, including diabetes
6. Mental disorder or poor compliance
7. Eating disorder or excessive use of alcohol, tobacco smoking or drug use
8. Past dose of radiation
9. 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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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11 participants in 3 patient groups

Adenosine

Active Comparator group

Description:

Perfusion is measured using PET/CT during intravenous infusion (0.14 mg/kg/min) of adenosine.

Treatment:

Drug: Adenosine

Room temperature

No Intervention group

Description:

Perfusion and A2A receptor density is measured using PET/CT in resting room temperature conditions.

Cold exposure

Experimental group

Description:

Perfusion and A2A receptor density is measured using PET/CT during controlled cold exposure.

Treatment:

Other: Cold exposure