CB1 Receptors in Human Brown Adipose Tissue

Not Applicable

Completed

• Conditions: Obesity
• Interventions: Other: Cold exposure; Other: [18F]FMPEP-d2; Other: [18F]FDG

• Registration Number: NCT02941172
• Lead Sponsor: Turku University Hospital

Brief Summary

This study investigates cannabinoid CB1 receptors in human brown adipose tissue (BAT) and other tissues using positron emission tomography (PET) imaging. Subjects will be scanned in room temperature conditions and during controlled cold exposure, and the density of CB1 receptors in BAT and other tissues will be quantified. The investigators hypothesize, that cannabinoid signaling is increased in cold conditions, when BAT is metabolically active.

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

Endocannabinoids have an important role in regulating energy balance and metabolism. Cannabinoid 1 receptors (CB1) are found in several tissues such as brown adipose tissue (BAT). Endocannabinoids and CB1 receptors participate in the control of lipid and glucose metabolism, and blockage of CB1 receptors has been found to improve metabolic factors linked to obesity and cardiovascular disease, making CB1 antagonists potential drugs against obesity and diabetes.

In this study the investigators use a PET radiotracer \[18F\]FMPEP-d2, which binds to CB1 receptors in vivo, to quantify the CB1 receptor density in BAT, white adipose tissue, muscle and the brain. This study is done once in warm conditions and once during controlled cold exposure. To verify whether the subject has metabolically active BAT, an additional PET scan with the radiotracer \[18F\]FDG is performed.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2016-10-19
• Study First Submitted QC: 2016-10-19
• Study First Posted: 2016-10-21
• Primary Completion: 2017-07-30
• Study Completion: 2017-12-30
• Status Verified: 2018-12
• Last Update Submitted: 2018-12-18
• Last Update Posted: 2018-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

• Healthy volunteer
• Group 1: BMI 20-26 kg/m2, Group2: BMI 27-40 kg/m2

Exclusion Criteria

• BMI < 20 kg/m2or BMI > 40 kg/m2
• Any chronic disease that could affect the study outcome, including medicated type 2 diabetes
• Mental disorder or poor compliance
• Eating disorder or excessive use of alcohol, tobacco smoking or drug use
• Past dose of radiation
• Presence of any ferromagnetic objects that would make MR imaging contraindicated
• 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
[18F]FDG in cold conditions	Cold exposure	PET scan is performed using PET radiotracer \[18F\]FDG during controlled cold exposure.
[18F]FMPEP-d2 in cold conditions	[18F]FMPEP-d2	PET scan is performed using PET radiotracer \[18F\]FMPEP-d2 during controlled cold exposure.
[18F]FMPEP-d2 in warm conditions	[18F]FMPEP-d2	PET scan is performed using PET radiotracer \[18F\]FMPEP-d2 in standard room temperature conditions.
[18F]FDG in cold conditions	[18F]FDG	PET scan is performed using PET radiotracer \[18F\]FDG during controlled cold exposure.
[18F]FMPEP-d2 in cold conditions	Cold exposure	PET scan is performed using PET radiotracer \[18F\]FMPEP-d2 during controlled cold exposure.

Primary Outcome Measures

Name	Time	Method
CB1 density of brown adipose tissue acquired with PET	within one study day	PET imaging is used to quantify CB1 receptors in tissues

Secondary Outcome Measures

Name	Time	Method
Glucose uptake of brown adipose tissue acquired with PET	within one study day	PET imaging is used to quantify glucose uptake in tissues

Trial Locations

Locations (1)

Turku PET Centre (Turku University Hospital); 🇫🇮 Turku, Finland