Adenosine and A2A Receptors in Human Brown Adipose Tissue

Not Applicable

Completed

• Conditions: Obesity
• Interventions: Other: Cold exposure; Drug: Adenosine

• Registration Number: NCT03327168
• Lead Sponsor: Turku University Hospital

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.

Study Timeline

• Study Start: 2015-11-01
• Primary Completion: 2016-06-30
• Study Completion: 2016-06-30
• Study First Submitted: 2017-09-28
• Status Verified: 2017-10
• Study First Submitted QC: 2017-10-26
• Study First Posted: 2017-10-31
• Last Update Submitted: 2017-10-31
• Last Update Posted: 2017-11-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 11

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cold exposure	Cold exposure	Perfusion and A2A receptor density is measured using PET/CT during controlled cold exposure.
Adenosine	Adenosine	Perfusion is measured using PET/CT during intravenous infusion (0.14 mg/kg/min) of adenosine.

Primary Outcome Measures

Name	Time	Method
BAT perfusion	Effect within 10 minutes	Perfusion of BAT with \[15O\]-H2O PET-CT
A2A receptor density in BAT	Effect within 3 hours	Density of A2A receptors in BAT measured with \[11C\]-TMSX PET/CT