CB1 Receptors in Human Brown Adipose Tissue

Study Overview
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Brief Summary
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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
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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.

Official Title
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Cannabinoid CB1 Receptors in Human Brown Adipose Tissue

Conditions
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Obesity

Intervention / Treatment
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* Other: Cold exposure
* Other: [18F]FMPEP-d2
* Other: [18F]FDG


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: [18F]FMPEP-d2 in warm conditions<br>PET scan is performed using PET radiotracer [18F]FMPEP-d2 in standard room temperature conditions. | Other: [18F]FMPEP-d2<br>* PET radiotracer used in imaging<br>|
| Other: [18F]FMPEP-d2 in cold conditions<br>PET scan is performed using PET radiotracer [18F]FMPEP-d2 during controlled cold exposure. | Other: Cold exposure<br>* Controlled cold exposure is performed before and during PET scan<br>Other: [18F]FMPEP-d2<br>* PET radiotracer used in imaging<br>|
| Other: [18F]FDG in cold conditions<br>PET scan is performed using PET radiotracer [18F]FDG during controlled cold exposure. | Other: Cold exposure<br>* Controlled cold exposure is performed before and during PET scan<br>Other: [18F]FDG<br>* PET radiotracer used in imaging<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brown adipose tissue, Cannabinoid receptor, PET imaging, Metabolism