Glucose Metabolism in Brown Adipose Tissue (BAT) in Young Healthy Men Evaluated by Deuterium Metabolic Imaging (DMI)

NCT04060745 | Terminated DMC

• 1 other identifier: Brown fat imaging
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

In this study the investigators wish to evaluate the glucose metabolism in brown adipose tissue (BAT) in young healthy men (aged 18-35). The investigators wish to validate a novel MR modality - Deuterium Metabolic Imaging (DMI), which is a non-radioactive, non-invasive method that allows for spatial as well as metabolic imaging after oral administration of deuterium-labelled glucose. Deuterium is a stable isotope of hydrogen that can be bound to different metabolites, in this case glucose. This method allows for metabolic imaging and production of 2H MR spectra of metabolites downstream from glucose uptake that can be quantified. DMI has not yet been used to evaluate BAT in humans. Currently, FDG PET/CT is the most widely used method for BAT evaluation in humans, but due to the radiation-exposure associated with FDG PET/CT repetitive studies of BAT in healthy subjects are limited. Therefore, new in vivo methods (preferably non-invasive) are warranted. However, since FDG PET/CT is the most widely used method, the investigators wish to use this modality as reference. The investigators plan to screen 10-12 subjects with an individualized cooling protocol and FDG PET/CT. Only the BAT positive subjects will be included in the DMI study. In the DMI study, the BAT positive subjects will enter in a randomized two-phased cross-over study. The subjects will have 2 DMI scans performed after ingestion of deuterium-labelled glucose; one after 2h of cooling, another in thermoneutrality. Primary outcome is the differences in glucose metabolites between cooling and thermoneutrality. The investigators hypothesize that during cooling uptake of glucose and its metabolites such as glutamine/glutamate and water may be enhanced. Moreover, glucose metabolism may shift towards anaerobic metabolism with increased lactate production as observed in a previous rodent study by the investigators group.

Conditions

Type2 Diabetes; Obesity; Metabolic Syndrome

Keywords

brown adipose tissue; deuterium metabolic imaging; FDG PET/CT; individualized cooling protocol

Outcome Measures

Primary Outcomes (4)

• Changes in glucose metabolism between non-activated and cold-activated BAT

  Changes measured by abundant \[2H\] labelled glucose signal in non-activated or cold-activated BAT compared to \[2H\] labelled glucose signal after \[2H\] labelled glucose ingestion. Delta \[2H\] labelled glucose signal in the two states will be compared by paired t-test

  1-2 weeks

• Changes in glucose metabolism between non-activated and cold-activated BAT

  Changes measured by abundant \[2H\] labelled lactate signal in non-activated or cold-activated BAT compared to \[2H\] labelled lactate signal after \[2H\] labelled glucose ingestion. Delta \[2H\] labelled lactate signal in the two states will be compared by paired t-test

  1-2 weeks

• Changes in glucose metabolism between non-activated and cold-activated BAT

  Changes measured by abundant \[2H\] labelled glutamate/glutamine signal in non-activated or cold-activated BAT compared to \[2H\] labelled glutamate/glutamine signal after \[2H\] labelled glucose ingestion. Delta \[2H\] labelled glutamate/glutamine signal in the two states will be compared by paired t-test

  1-2 weeks

• Changes in glucose metabolism between non-activated and cold-activated BAT

  Changes measured by abundant \[2H\] labelled water signal in non-activated or cold-activated BAT compared to \[2H\] labelled water signal after \[2H\] labelled glucose ingestion. Delta \[2H\] labelled water signal in the two states will be compared by paired t-test

  1-2 weeks

Secondary Outcomes (8)

• BAT DMI measurements compared to plasma NMR measurements

  1-2 weeks

• BAT DMI measurements compared to plasma NMR measurements

  1-2 weeks

• BAT DMI measurements compared to plasma NMR measurements

  1-2 weeks

• BAT DMI measurements compared to plasma NMR measurements

  1-2 weeks

• Changes in fat/water thresholds in BAT in cold versus thermoneutral conditions

  1-2 weeks

Study Arms (2)

Cooling

EXPERIMENTAL

Participants will be cooled using an individualized cooling protocol with a water-perfused vest for two hours while resting. Afterwards, participants will drink 75g of D2-glucose dissolved in water and DMI will be performed.

Other: cooling using a water-perfused vest

Thermoneutrality

EXPERIMENTAL

Participants will rest for one hours. Afterwards, participants will drink 75g of D2-glucose dissolved in water and DMI will be performed.

Other: thermoneutrality

Interventions

cooling using a water-perfused vest OTHER

BAT is activated by cold exposure. Each participant will have a shivering threshold test performed before entering the cooling arm. Participants will be gradually cooled (decreasing the temperature in the cooling vest by 0.6C every 15 min. until 3.8C) using a perfused cooling vest until they start to shiver. The temperature in which they start to shiver will be noted. If shivering has not occurred at 3.8C after 15 min. they will stay at the temperature for 45 min. in total or until shivering occurs. Shivering is defined by subjective perception of shivering by the participant in a numeric scale (NRS) where "0" refers to "I'm not shivering" and 10 refers to "I'm shivering a lot" and visual inspection by the investigator. The temperature used in the cooling arm will be set a few degrees above the shivering threshold test or at 3.8C if shivering did not occur. During cooling indirect calorimetry and OGTT will be performed and finally the DMI scan will be performed

Also known as: Indirect calorimetry, oral glucose tollearnce test (OGTT), DMI scan

Cooling

thermoneutrality OTHER

In the thermoneutrality arm participants will rest in thermoneutrality (22C) for one hour. Before the DMI scan indirect calorimetry will be performed

Also known as: Indirect calometry, DMI scan

Thermoneutrality

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy young men (aged 18-35), body mass index (BMI) 18.5-25, weight change ˂ 5% in the last 6 months

You may not qualify if:

• acute or chronic disease, regular medication that could influence the cardiovascular or thermoregulatory response, alcohol intake ˃ 21 units/week, claustrophobia, pacemaker or metal devices in the body and smoking.

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator
• Steno Diabetes Center Copenhagen: collaborator

Study Sites (1)

Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Aarhus, 8200, Denmark

Location

MeSH Terms

Conditions

Obesity; Metabolic Syndrome

Interventions

Calorimetry, Indirect

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Calorimetry; Chemistry Techniques, Analytical; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be screened for active brown adipose tissue (BAT) using FDG PET/CT. Only BAT-positive participants will enter the two-phased randomized crossover trial using DMI under cold or thermoneutral conditions

Study Record Dates

• First Submitted: August 8, 2019
• First Posted: August 19, 2019
• Study Start: August 1, 2019
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: June 7, 2024

Record last verified: 2021-05

Locations

DK (1)