Effects of Fructose/Glucose-rich Diet on Brown Fat in Healthy Subjects (GB7) (GB7)

January 22, 2025 updated by: André Carpentier, Université de Sherbrooke

Brown Fat Energy Metabolism During Cold Exposure: Effects of Fructose- or Glucose-rich Diet in Healthy Subjects

Activating brown and beige adipose tissue (herein described as BAT) has been recently recognized as a potential means to increase energy expenditure and lower blood glucose, however, BAT activity appears to be reduced with obesity, aging or Type 2 Diabetes (T2D). BAT has the unique capability to burn large amounts of sugar and fat and effectively dissipate this energy as heat due to the expression of uncoupling protein 1 (UCP1) which is controlled by a thermogenic gene program of transcription factors, co-activators and protein kinases. Thus, enhancing the thermogenic gene program may be beneficial for treating obesity and T2D. Despite the importance of BAT in regulating metabolism our understanding of the factors which suppress its metabolic activity with obesity, aging and T2D are largely unknown. Recently, it was shown that peripheral serotonin, which is regulated by the tryptophan hydroxylase 1 (Tph1), is a negative regulator of BAT metabolic activity. In addition to serotonin, other studies have indicated that pro-inflammatory stimuli may also inhibit BAT metabolic activity. These data suggest that reduced activation of BAT may be due to increases in peripheral serotonin and inflammation. Importantly, the gut microbiome has recently been recognized as an important regulator of serotonin and inflammatory pathways suggesting the observed effects of the microbiome on obesity, T2D may be mediated in part through reductions in BAT activity.

One mechanism by which the environment may impact BAT activity and the thermogenic gene program over the last 3 decades involves changes in our food supply as result of changes in agricultural production (chlorpyrifos, glyphosphate) and the addition of food additives (fructose). These agents have been reported to alter inflammation, serotonin metabolism and the gut microbiome indicating a potential bimodal (direct and indirect via the microbiome) mechanism by which they may alter the thermogenic gene program and contribute to chronic metabolic disease. Thus, our overarching hypothesis is that environmental agents and additives related to food production may contribute to the reduced metabolic activity of BAT. The objective is to identify and characterize how food production agents and additives reduce the metabolic activity of BAT.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Each subject will follow 3 metabolic studies (A, B and C), each lasting 7.5h which includes a 3h acute cold exposure.

These studies will be almost identical: same perfusion of tracers, same number of Positron Emission Tomography (PET) acquisitions and same number of Magnetic Resonance Imaging (MRI) associated with Magnetic Resonance Spectroscopy (MRS) acquisitions .

The difference will be in the diet ingested by the subjects two weeks before each metabolic study: during protocol A, the subjects will follow an isocaloric diet; during protocol B, the subjects will follow the same isocaloric diet supplemented with a daily beverage containing +25% of energy intake from fructose; and during protocol C, the subjects will follow the same isocaloric diet supplemented with a daily beverage containing +25% of energy intake from glucose.

Stool samples will be collected for each metabolic study for microbiome flora and metabolites.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Centre de Recherche du CHUS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Healthy subjects: subjects with normal glucose tolerance determined according to an oral glucose tolerance test and with a BMI < 27 kg/m2 without first degree of familial history of type 2 diabetes (parents, siblings).

Exclusion Criteria:

  1. Plasma triglycerides > 5.0 mmol/L at fasting;
  2. More than 2 alcohol consumption per day;
  3. More than 1 cigarette per day;
  4. History of total cholesterol level > 7 mmol/L, of cardiovascular disease, hypertensive crisis;
  5. Treatment with fibrates, thiazolidinedione, insulin, beta-blockers or other drugs with effects on insulin resistance or lipid metabolism (exception for anti-hypertensive drugs, statins or metformin);
  6. Presence of a non-controlled thyroid disease, renal or hepatic disease, history of pancreatitis, bleeding diatheses, cardiovascular disease or any other serious medical conditions;
  7. History of serious gastrointestinal disorders (malabsorption, peptic ulcer, gastroesophageal reflux having required a surgery, etc.);
  8. Presence of a pacemaker;
  9. Have undergone of PET study or CT scan in the past year;
  10. Chronic administration of any medication;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Isocaloric Diet
Two weeks of isocaloric diet
Other: cold exposure
Acute cold exposure using a water-conditioned cooling suit will be applied from time 0 to 180 min. At the same time mean skin temperature will be measured by 11 thermocouples.
Radiation: 18FDG
I.v. injection of 18-fluorodeoxyglucose (18FDG) will be performed, followed by 30 min dynamic and 50 min wholebody PET/CT scanning.
Radiation: 11C-acetate
i.v. injection of 11C-acetate will be performed, followed by 20 min dynamic PET/CT scanning
Radiation: [3-3H]-glucose
i.v. administration of 1.5 uCi/min of [3-3H]-glucose
Other: [U-13C]-palmitate
i.v. administration of 0.08 umol/kg/min of [U-13C]-palmitate
Other: 2H-Glycerol
i.v. administration of 0.05 µmol/kg/min of 2H-glycerol
Device: MRI/MRS
Visceral and cervico-thoracic MRI and MRS acquisition.
Device: Electromyogram (EMG)
Skeletal muscle activity and shivering intensity will be measured by electromyography using surface electrodes
Device: DXA
Lean mass will be determined by dual-energy X-ray absorptiometry
Device: Indirect calorimetry
VCO2 will be measured by indirect calorimetry between 15 and 20 min every hour until time 180.
Other: Fructose diet
Two weeks of hypercaloric diet supplemented with fructose
Other: cold exposure
Acute cold exposure using a water-conditioned cooling suit will be applied from time 0 to 180 min. At the same time mean skin temperature will be measured by 11 thermocouples.
Radiation: 18FDG
I.v. injection of 18-fluorodeoxyglucose (18FDG) will be performed, followed by 30 min dynamic and 50 min wholebody PET/CT scanning.
Radiation: 11C-acetate
i.v. injection of 11C-acetate will be performed, followed by 20 min dynamic PET/CT scanning
Radiation: [3-3H]-glucose
i.v. administration of 1.5 uCi/min of [3-3H]-glucose
Other: [U-13C]-palmitate
i.v. administration of 0.08 umol/kg/min of [U-13C]-palmitate
Other: 2H-Glycerol
i.v. administration of 0.05 µmol/kg/min of 2H-glycerol
Device: MRI/MRS
Visceral and cervico-thoracic MRI and MRS acquisition.
Device: Electromyogram (EMG)
Skeletal muscle activity and shivering intensity will be measured by electromyography using surface electrodes
Device: DXA
Lean mass will be determined by dual-energy X-ray absorptiometry
Device: Indirect calorimetry
VCO2 will be measured by indirect calorimetry between 15 and 20 min every hour until time 180.
Dietary supplement: Diet
A 2 weeks of hypercaloric diet supplemented with fructose or glucose
Other: Glucose diet
Two weeks of hypercaloric diet supplemented with glucose
Other: cold exposure
Acute cold exposure using a water-conditioned cooling suit will be applied from time 0 to 180 min. At the same time mean skin temperature will be measured by 11 thermocouples.
Radiation: 18FDG
I.v. injection of 18-fluorodeoxyglucose (18FDG) will be performed, followed by 30 min dynamic and 50 min wholebody PET/CT scanning.
Radiation: 11C-acetate
i.v. injection of 11C-acetate will be performed, followed by 20 min dynamic PET/CT scanning
Radiation: [3-3H]-glucose
i.v. administration of 1.5 uCi/min of [3-3H]-glucose
Other: [U-13C]-palmitate
i.v. administration of 0.08 umol/kg/min of [U-13C]-palmitate
Other: 2H-Glycerol
i.v. administration of 0.05 µmol/kg/min of 2H-glycerol
Device: MRI/MRS
Visceral and cervico-thoracic MRI and MRS acquisition.
Device: Electromyogram (EMG)
Skeletal muscle activity and shivering intensity will be measured by electromyography using surface electrodes
Device: DXA
Lean mass will be determined by dual-energy X-ray absorptiometry
Device: Indirect calorimetry
VCO2 will be measured by indirect calorimetry between 15 and 20 min every hour until time 180.
Dietary supplement: Diet
A 2 weeks of hypercaloric diet supplemented with fructose or glucose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Microbiome flora
Time Frame: 4 months
assessed from stool samples
4 months
Microbiome metabolites
Time Frame: 4 months
assessed from stool samples
4 months
BAT oxidative metabolism
Time Frame: 4 months
will be determined using i.v. injection of 11C-acetate during dynamic PET/CT scanning
4 months
BAT triglyceride content
Time Frame: 4 months
will be determined by radiodensity or MRS
4 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
energy metabolism (whole body production)
Time Frame: 4 months
by indirect calorimetry
4 months
BAT blood flow
Time Frame: 4 months
will be determined using i.v. injection of 11C-acetate during dynamic PET/CT scanning
4 months
BAT net glucose uptake
Time Frame: 4 months
will be assessed using i.v. injection of 18FDG with sequential dynamic PET/CT scanning.
4 months
Whole-body glucose partitioning
Time Frame: 4 months
will be assessed using i.v. injection of 18FDG with static PET/CT scanning
4 months
BAT volume of metabolic activity
Time Frame: 4 months
will be determined using a total body CT (16 mA) followed by a PET acquisition
4 months
metabolites appearance rate
Time Frame: 12 months
will be determined by perfusion of stable isotope tracers
12 months
hormonal responses
Time Frame: 12 months
analysed by colorimetric and Elisa tests
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Université de Sherbrooke

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
McMaster University
University of Ottawa

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: André C. Carpentier, Université de Sherbrooke

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 23, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 17, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 13, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 15, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 22, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2017-1459

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type2 Diabetes

Clinical Trials on cold exposure

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings