Brown Adipose Tissue Metabolism in Type 2 Diabetes (GB8)

Université de Sherbrooke

Status: Enrolling

Conditions: Type 2 Diabetes

Treatments: Drug: Oral Nicotinic acid; Other: Cold exposure

Study type: Interventional

Funder types: Other

Identifiers

NCT05092945

2019-2990

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 4 patient groups

Subject with Type 2 Diabetes- cold exposure

Active Comparator group

Description:

3-hour cold exposure: Protocol B

Treatment:

Other: Cold exposure

Subject with type 2 Diabetes- cold exposure and nicotinic acid

Experimental group

Description:

3-hour cold exposure with oral nicotinic acid: Protocol A

Treatment:

Other: Cold exposure

Drug: Oral Nicotinic acid

Subject without Type 2 Diabetes- cold exposure

Active Comparator group

Description:

3-hour cold exposure: Protocol B

Treatment:

Other: Cold exposure

Subject without type 2 Diabetes- cold exposure and nicotinic acid

Experimental group

Description:

3-hour cold exposure with oral nicotinic acid: Protocol A

Treatment:

Other: Cold exposure

Drug: Oral Nicotinic acid