Clinical trial NCT05092945: Brown Adipose Tissue Metabolism in Type 2 Diabetes
Official title: Quantifying Brown Adipose Tissue Thermogenesis in Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
First posted: 2021-10-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two groups in parallel (with and without Type 2 diabetes). In each group, the protocol will be carried out as a within-subject, randomized, cross-over study in which each subject will serve as his/her own control.
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: BAT volume
timeFrame: 180 minutes after the start of the cold exposure
measure: Brown Adipose Tissue (BAT) Glucose uptake
timeFrame: 150 minutes after the start of the cold exposure
Secondary outcomes:
measure: Activation of BAT (oxidative metabolism)
timeFrame: 90 minutes after beginning cold exposure
measure: Fatty Acid uptake and metabolism
timeFrame: at baseline and at time 120 minutes after beginning cold exposure
measure: BAT triglyceride content
timeFrame: at baseline and at time 180 (for CT) and 240 (for MR) after cold exposure.
measure: Whole-body lipolysis
timeFrame: -150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.
measure: Hepatic Glucose production
timeFrame: -150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.
measure: Substrate utilisation
timeFrame: -150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.
measure: Changes in insulin level and secretion
timeFrame: -150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Centre de recherche du CHUS
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: André Carpentier
role: PRINCIPAL_INVESTIGATOR
References: