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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Adenosine; Other: Cold exposure

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Collaborators: University of Bonn
• Investigators: Principal Investigator: Kirsi A Virtanen, MD, PhD, Turku University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): June 30, 2016
• Study Completion (Actual): June 30, 2016

Study Registration Dates

• First Submitted: September 28, 2017
• First Submitted That Met QC Criteria: October 26, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Adipose Tissue, Brown
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine
• Other Study ID Numbers: T201/2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No