Type2 DiabetesGB7NCT03188835
Effects of Fructose/Glucose-rich Diet on Brown Fat in Healthy Subjects (GB7)
A study testing Diet, cold exposure and 18FDG in people with Type2 Diabetes, run by Université de Sherbrooke at 1 site in Canada.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 20 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Type2 Diabetes
- What is being tested?
- Diet, cold exposure and 18FDG
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 23 May 2017to 30 Apr 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- Plasma triglycerides > 5.0 mmol/L at fasting;
- More than 2 alcohol consumption per day;
- More than 1 cigarette per day;
- History of total cholesterol level > 7 mmol/L, of cardiovascular disease, hypertensive crisis;
- 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);
- Presence of a non-controlled thyroid disease, renal or hepatic disease, history of pancreatitis, bleeding diatheses, cardiovascular disease or any other serious medical conditions;
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- History of serious gastrointestinal disorders (malabsorption, peptic ulcer, gastroesophageal reflux having required a surgery, etc.);
- Presence of a pacemaker;
- Have undergone of PET study or CT scan in the past year;
- Chronic administration of any medication;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Type2 Diabetes
- Being tested
- Diet, cold exposure, 18FDG, 11C-acetate, [3-3H]-glucose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DietDietary supplement
A 2 weeks of hypercaloric diet supplemented with fructose or glucose
cold exposureOther
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.
18FDGRadiation
I.v. injection of 18-fluorodeoxyglucose (18FDG) will be performed, followed by 30 min dynamic and 50 min wholebody PET/CT scanning.
11C-acetateRadiation
i.v. injection of 11C-acetate will be performed, followed by 20 min dynamic PET/CT scanning
[3-3H]-glucoseRadiation
i.v. administration of 1.5 uCi/min of [3-3H]-glucose
[U-13C]-palmitateOther
i.v. administration of 0.08 umol/kg/min of [U-13C]-palmitate
2H-GlycerolOther
i.v. administration of 0.05 µmol/kg/min of 2H-glycerol
MRI/MRSDevice
Visceral and cervico-thoracic MRI and MRS acquisition.
Electromyogram (EMG)Device
Skeletal muscle activity and shivering intensity will be measured by electromyography using surface electrodes
DXADevice
Lean mass will be determined by dual-energy X-ray absorptiometry
Indirect calorimetryDevice
VCO2 will be measured by indirect calorimetry between 15 and 20 min every hour until time 180.
| Study group | Role | What they receive |
|---|---|---|
| Isocaloric Diet | Other | Two weeks of isocaloric diet Receives: Other: cold exposure; Radiation: 18FDG; Radiation: 11C-acetate; Radiation: [3-3H]-glucose; Other: [U-13C]-palmitate; Other: 2H-Glycerol; Device: MRI/MRS; Device: Electromyogram (EMG); Device: DXA; Device: Indirect calorimetry |
| Fructose diet | Other | Two weeks of hypercaloric diet supplemented with fructose Receives: Dietary Supplement: Diet; Other: cold exposure; Radiation: 18FDG; Radiation: 11C-acetate; Radiation: [3-3H]-glucose; Other: [U-13C]-palmitate; Other: 2H-Glycerol; Device: MRI/MRS; Device: Electromyogram (EMG); Device: DXA; Device: Indirect calorimetry |
| Glucose diet | Other | Two weeks of hypercaloric diet supplemented with glucose Receives: Dietary Supplement: Diet; Other: cold exposure; Radiation: 18FDG; Radiation: 11C-acetate; Radiation: [3-3H]-glucose; Other: [U-13C]-palmitate; Other: 2H-Glycerol; Device: MRI/MRS; Device: Electromyogram (EMG); Device: DXA; Device: Indirect calorimetry |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microbiome flora
assessed from stool samples
Measured: 4 months
Microbiome metabolites
assessed from stool samples
Measured: 4 months
BAT oxidative metabolism
will be determined using i.v. injection of 11C-acetate during dynamic PET/CT scanning
Measured: 4 months
BAT triglyceride content
will be determined by radiodensity or MRS
Measured: 4 months
Secondary outcomes (7)
BAT blood flow
will be determined using i.v. injection of 11C-acetate during dynamic PET/CT scanning
Measured: 4 months
BAT net glucose uptake
will be assessed using i.v. injection of 18FDG with sequential dynamic PET/CT scanning.
Measured: 4 months
Whole-body glucose partitioning
will be assessed using i.v. injection of 18FDG with static PET/CT scanning
Measured: 4 months
BAT volume of metabolic activity
will be determined using a total body CT (16 mA) followed by a PET acquisition
Measured: 4 months
metabolites appearance rate
will be determined by perfusion of stable isotope tracers
Measured: 12 months
energy metabolism (whole body production)
by indirect calorimetry
Measured: 4 months
hormonal responses
analysed by colorimetric and Elisa tests
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2017
- Study start23 May 2017
- Primary completion17 Dec 2020
- Study completion30 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type2 DiabetesStudies of the same condition, open and under way.
- More trials run by Université de SherbrookeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- McMaster University, University of Ottawa
- Responsible party
- Principal investigator, André Carpentier, Université de Sherbrooke
- Investigators
- André C. Carpentier, Principal investigator, Université de Sherbrooke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03188835
- Sponsor's protocol ID
- 2017-1459
- Acronym
- GB7
- Status last verified
- Jan 2025
- First submitted
- 13 Jun 2017
- Last updated
- 27 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Richard G, Blondin DP, Syed SA, Rossi L, Fontes ME, Fortin M, Phoenix S, Frisch F, Dubreuil S, Guerin B, Turcotte EE, Lepage M, Surette MG, Schertzer JD, Steinberg GR, Morrison KM, Carpentier AC. High-fructose feeding suppresses cold-stimulated brown adipose tissue glucose uptake independently of changes in thermogenesis and the gut microbiome. Cell Rep Med. 2022 Sep 20;3(9):100742. doi: 10.1016/j.xcrm.2022.100742.
PubMed 36130480
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brown Fat Energy Metabolism During Cold Exposure: Effects of Fructose- or Glucose-rich Diet in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03188835
- Acronym / sponsor ID
- GB7 / 2017-1459
- Conditions
- Type2 Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Université de SherbrookeUniversity, hospital or other
- Collaborators
- McMaster University, University of Ottawa
- Study start
- 23 May 2017 (actual)
- Primary completion
- 17 Dec 2020 (actual)
- Study completion
- 30 Apr 2021 (actual)
- First posted
- 15 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Isocaloric Diet | Other | Other: cold exposure, Radiation: 18FDG, Radiation: 11C-acetate, Radiation: [3-3H]-glucose, Other: [U-13C]-palmitate, Other: 2H-Glycerol, Device: MRI/MRS, Device: Electromyogram (EMG), Device: DXA, Device: Indirect calorimetryTwo weeks of isocaloric diet |
| Fructose diet | Other | Dietary Supplement: Diet, Other: cold exposure, Radiation: 18FDG, Radiation: 11C-acetate, Radiation: [3-3H]-glucose, Other: [U-13C]-palmitate, Other: 2H-Glycerol, Device: MRI/MRS, Device: Electromyogram (EMG), Device: DXA, Device: Indirect calorimetryTwo weeks of hypercaloric diet supplemented with fructose |
| Glucose diet | Other | Dietary Supplement: Diet, Other: cold exposure, Radiation: 18FDG, Radiation: 11C-acetate, Radiation: [3-3H]-glucose, Other: [U-13C]-palmitate, Other: 2H-Glycerol, Device: MRI/MRS, Device: Electromyogram (EMG), Device: DXA, Device: Indirect calorimetryTwo weeks of hypercaloric diet supplemented with glucose |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 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).
Key exclusion criteria (10 listed)
- Plasma triglycerides > 5.0 mmol/L at fasting;
- More than 2 alcohol consumption per day;
- More than 1 cigarette per day;
- History of total cholesterol level > 7 mmol/L, of cardiovascular disease, hypertensive crisis;
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DietA 2 weeks of hypercaloric diet supplemented with fructose or glucose | Dietary supplement | Fructose diet, Glucose diet |
| cold exposureAcute 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. | Other | Fructose diet, Glucose diet, Isocaloric Diet |
| 18FDGI.v. injection of 18-fluorodeoxyglucose (18FDG) will be performed, followed by 30 min dynamic and 50 min wholebody PET/CT scanning. | Radiation | Fructose diet, Glucose diet, Isocaloric Diet |
| 11C-acetatei.v. injection of 11C-acetate will be performed, followed by 20 min dynamic PET/CT scanning | Radiation | Fructose diet, Glucose diet, Isocaloric Diet |
| [3-3H]-glucosei.v. administration of 1.5 uCi/min of [3-3H]-glucose | Radiation | Fructose diet, Glucose diet, Isocaloric Diet |
| [U-13C]-palmitatei.v. administration of 0.08 umol/kg/min of [U-13C]-palmitate | Other | Fructose diet, Glucose diet, Isocaloric Diet |
| 2H-Glyceroli.v. administration of 0.05 µmol/kg/min of 2H-glycerol | Other | Fructose diet, Glucose diet, Isocaloric Diet |
| MRI/MRSVisceral and cervico-thoracic MRI and MRS acquisition. | Device | Fructose diet, Glucose diet, Isocaloric Diet |
| Electromyogram (EMG)Skeletal muscle activity and shivering intensity will be measured by electromyography using surface electrodes | Device | Fructose diet, Glucose diet, Isocaloric Diet |
| DXALean mass will be determined by dual-energy X-ray absorptiometry | Device | Fructose diet, Glucose diet, Isocaloric Diet |
| Indirect calorimetryVCO2 will be measured by indirect calorimetry between 15 and 20 min every hour until time 180. | Device | Fructose diet, Glucose diet, Isocaloric Diet |
Primary outcome
Microbiome flora
Time frame: 4 months
assessed from stool samples
Microbiome metabolites
Time frame: 4 months
assessed from stool samples
BAT oxidative metabolism
Time frame: 4 months
will be determined using i.v. injection of 11C-acetate during dynamic PET/CT scanning
BAT triglyceride content
Time frame: 4 months
will be determined by radiodensity or MRS
7 secondary outcomes
BAT blood flow
Time frame: 4 months
BAT net glucose uptake
Time frame: 4 months
Whole-body glucose partitioning
Time frame: 4 months
BAT volume of metabolic activity
Time frame: 4 months
metabolites appearance rate
Time frame: 12 months
energy metabolism (whole body production)
Time frame: 4 months
hormonal responses
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2025.
- Derived from this study: PubMed 36130480Richard G, Blondin DP, Syed SA, Rossi L, Fontes ME, Fortin M, Phoenix S, Frisch F, Dubreuil S, Guerin B, Turcotte EE, Lepage M, Surette MG, Schertzer JD, Steinberg GR, Morrison KM, Carpentier AC. High-fructose feeding suppresses cold-stimulated brown adipose tissue glucose uptake independently of changes in thermogenesis and the gut microbiome. Cell Rep Med. 2022 Sep 20;3(9):100742. doi: 10.1016/j.xcrm.2022.100742.
- High-fructose feeding suppresses cold-stimulated brown adipose tissue glucose uptake independently of changes in thermogenesis and the gut microbiomeLink provided by the sponsor.
- Human brown adipose tissue is not enough to combat cardiometabolic diseasesLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
André C. Carpentier principal investigator
Université de Sherbrooke
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Diet, cold exposure and 18FDG in people with Type2 Diabetes, run by Université de Sherbrooke at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Microbiome flora (time frame: 4 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03188835, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2025.