CB1 Receptors in Human Brown Adipose Tissue (CANBAT)

Cannabinoid CB1 Receptors in Human Brown Adipose Tissue

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: [18F]FMPEP-d2; Other: Cold exposure; Other: [18F]FDG

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland, 20521
    • Turku PET Centre (Turku University Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 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
Other: [18F]FMPEP-d2 in warm conditions; PET scan is performed using PET radiotracer [18F]FMPEP-d2 in standard room temperature conditions.	Other: [18F]FMPEP-d2; PET radiotracer used in imaging
Other: [18F]FMPEP-d2 in cold conditions; PET scan is performed using PET radiotracer [18F]FMPEP-d2 during controlled cold exposure.	Other: [18F]FMPEP-d2; PET radiotracer used in imaging; Other: Cold exposure; Controlled cold exposure is performed before and during PET scan
Other: [18F]FDG in cold conditions; PET scan is performed using PET radiotracer [18F]FDG during controlled cold exposure.	Other: Cold exposure; Controlled cold exposure is performed before and during PET scan; Other: [18F]FDG; PET radiotracer used in imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CB1 density of brown adipose tissue acquired with PET	PET imaging is used to quantify CB1 receptors in tissues	within one study day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose uptake of brown adipose tissue acquired with PET	PET imaging is used to quantify glucose uptake in tissues	within one study day

Collaborators and Investigators

• Sponsor: Turku University Hospital

Publications and helpful links

General Publications

• Lahesmaa M, Eriksson O, Gnad T, Oikonen V, Bucci M, Hirvonen J, Koskensalo K, Teuho J, Niemi T, Taittonen M, Lahdenpohja S, U Din M, Haaparanta-Solin M, Pfeifer A, Virtanen KA, Nuutila P. Cannabinoid Type 1 Receptors Are Upregulated During Acute Activation of Brown Adipose Tissue. Diabetes. 2018 Jul;67(7):1226-1236. doi: 10.2337/db17-1366. Epub 2018 Apr 12.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): July 30, 2017
• Study Completion (Actual): December 30, 2017

Study Registration Dates

• First Submitted: October 19, 2016
• First Submitted That Met QC Criteria: October 19, 2016
• First Posted (Estimate): October 21, 2016

Study Record Updates

• Last Update Posted (Actual): December 20, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: PET imaging; Metabolism; Brown adipose tissue; Cannabinoid receptor
• Other Study ID Numbers: 42/2014

Plan for Individual participant data (IPD)

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