Brown Adipose Tissue Metabolism in Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— GB8  

Official title:

Quantifying Brown Adipose Tissue Thermogenesis in Type 2 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05092945
• Other study ID #: 2019-2990
• Status: Recruiting
• Phase: N/A
• Start date: May 18, 2021
• Est. completion date: March 2025

Study information

• Verified date: November 2023
• Source: Université de Sherbrooke
• Contact: Frédérique Frisch
• Phone: 819-346-1110
• Email: frederique.frisch[@]Usherbrooke.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Activation of brown adipose tissue (BAT) by cold exposure. BAT thermogenesis and BAT volume of metabolic activity will be assessed by Positron-Emitting-Tomography (PET/CT) and MRI/MRS imaging and new pharmacological methods to modulate BAT thermogenesis. All previous data on the functioning of Brown Adipose Tissue (BAT) were obtained by Positron-Emitting-Tomography (PET) imaging studies using fluorodeoxyglucose F18 ( [18F]- FDG). This approach underestimates the actual activity of the BAT. In this study, the investigator is going to use a new PET tracer (C11-palmitate) which is a fat molecule. This will allow to quantify more accurately the activity of brown fat.

Description:

The study protocol includes three visits: the screening visit (V1) and two PET/MRI imaging studies (V2 and V3) performed in random order at an interval of 7 to 14 days. PET/ MRI studies will be performed with and without nicotinic acid. A total of 500 mg of nicotinic acid will be given orally, at a rate of 2 doses of 150 mg and 2 doses of 100 mg, through V2 (protocol A): one dose at time 0, 60 minutes, 120 minutes and 180 minutes. During V2 and V3, participants will undergo Acute Cold Exposure to stimulate brown adipose tissue. The morning of each PET imaging study, the participants will follow an MRI acquisition to determine hepatic, pancreatic, visceral and BAT lipid content, followed by an MRS acquisition in the hepatic and cervico-thoracic region. MRI and MRS acquisition of the hepatic and cervico-thoracic region will be repeated again at the end of the day. The radioactive PET tracers used in this study are the [11C]-acetate, [11C]-palmitate and [18F]-FDG followed by dynamic and whole-body scans. Stable isotopes such as [U-13C]-palmitate (0.08 umol/kg/min), 5D-glycérol (0.1 µmol/kg/min,) and tritiated glucose (of 1.5 uCi/min) will be perfused from the start of the day until time 180 min.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 10 men and 10 women with T2D.
• 10 non-diabetic men and 10 non-diabetic women (matched for sex, BMI and age to the T2D participants).

Exclusion Criteria:

• Change in weight of more than 2 kg over the past 3 months or recent changes in lifestyle;
• Treatment with a fibrate, thiazolidinedione, insulin, beta-blocker, GLP-1 agonist, or other drug known to affect lipid or carbohydrate metabolism, except statins, metformin, sulfonylurea, DPP-IV inhibitor and other antihypertensive agents that can be temporarily stopped safely prior to the studies, as per our approved protocols;
• Presence of overt cardiovascular, liver, renal or other medical conditions;
• Smoking or consumption of more than 2 alcoholic beverages per day;
• Any other contraindication to temporarily suspending current medications for lipids or hypertension;
• Any contraindication to MRI scanning.
• Having participated to a research study with exposure to radiation in the last two years before the start of the study.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Other:
• Cold exposure
The liquid-conditioned tube suit will be perfused with 18°C water using a temperature- and flow-controlled circulation bath from time 0 to 180 min.

Drug:
• Oral Nicotinic acid
A total of 500 mg of nicotinic acid will be given orally, at a rate of 2 doses of 150 mg and 2 doses of 100 mg: one dose of 150 mg at time 0 and 60 minutes, one dose of 100 mg at time 120 minutes and 180 minutes.

Locations

Country	Name	City	State
Canada	Centre de recherche du CHUS	Sherbrooke	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Université de Sherbrooke

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BAT volume	Assessed using i.v. injection of 18FDG with whole-body PET/CT acquisition.	180 minutes after the start of the cold exposure
Primary	Brown Adipose Tissue (BAT) Glucose uptake	Assessed using i.v. injection of 18FDG with sequential dynamic PET/CT scanning	150 minutes after the start of the cold exposure
Secondary	Activation of BAT (oxidative metabolism)	Measured with 11C-acetate using dynamic PET/CT acquisition.	90 minutes after beginning cold exposure
Secondary	Fatty Acid uptake and metabolism	Measured with 11C-palmitate using dynamic PET/CT acquisition.	at baseline and at time 120 minutes after beginning cold exposure
Secondary	BAT triglyceride content	Estimated by CT and MR using 1H-MRS and Dixon sequences on a 3T clinical MRI system.	at baseline and at time 180 (for CT) and 240 (for MR) after cold exposure.
Secondary	Whole-body lipolysis	Systemic appearance rate of glycerol and fatty acid determined by perfusion of [1,1,2,3,3-2H]-glycerol, [U-13C]-palmitate tracers and concentration of total NEFA, triglycerides, palmitate, oleate, linoleate, glycerol.	-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.
Secondary	Hepatic Glucose production	Systemic appearance rate of glucose determined by perfusion of [3-3H]-glucose.	-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.
Secondary	Substrate utilisation	VO2 and VCO2 will be measured by indirect calorimetry to calculate carbohydrate and fatty acid oxidation rates.	-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.
Secondary	Changes in insulin level and secretion	measured with ELISA and Milliplex.	-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.