Type 2 DiabetesGB9NCT04823442
Activation of Brown Adipose Tissue Metabolism Using Mirabegron
A study testing Mirabegron and Bisoprolol Fumarate in people with Type 2 Diabetes, run by Université de Sherbrooke at 1 site in Canada.
Trial summary
Could sympathomimetics and sympatholytics drugs safe for the management of Type 2 Diabetes (T2D)? Based on recent evidence, we propose that pharmacological stimulation of Beta-3 adrenergic receptor (ADBR3) at higher doses of Mirabegron may be required to elicit changes in glycemia, but should be combined with Beta-1… Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Mirabegron and Bisoprolol Fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteCanada
- Study dates
- 21 Jan 2021to 4 Apr 2022
- 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 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects with normal glucose tolerance determined according to an oral glucose tolerance test;
- BMI ≤ 30 kg/m2.
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,betablockers or other drugs with effects on insulin resistance or lipid metabolism (exception for antihypertensive drugs, statins or metformin);
- Presence of a noncontrolled 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.); 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: Sympathomimetics and Sympatholytics in Type 2 Diabetes: Teaching Old Drugs New Tricks
Could sympathomimetics and sympatholytics drugs safe for the management of Type 2 Diabetes (T2D)? Based on recent evidence, we propose that pharmacological stimulation of Beta-3 adrenergic receptor (ADBR3) at higher doses of Mirabegron may be required to elicit changes in glycemia, but should be combined with Beta-1 adrenergic receptor (ADRB1) antagonists to suppress the unwanted effects on the cardiovascular system.
Together, several results establish a previously unappreciated cross-talk between Gs-coupled ADRB1 and ADRB3 in adipose tissue for the control of glucose homeostasis. Moreover, these data suggest that antagonizing ADRB1 may be a good way to significantly lower the dose of ADRB3 agonist required for glucose control.
Therefore, we believe that there are therapeutic opportunities in targeting adrenergic receptors for the treatment of T2D at least in young/middle aged people.
Read the detailed description
In brief, participants will take part in 2 metabolic studies (A and B) performed in random order and at an interval of 7 to 14 days. Each metabolic study will last 8.5 hours with a baseline period of 2.5 hours. Participants will ingest either 200 mg of the ADRB3 agonist mirabegron (Myrbetriq, Astellas Pharma Canada) alone (study A) or in combination with 10 mg of bisoprolol, an ADRB1-antagonist (study B), at time 0.
The radioactive PET tracers (PET: positron emission tomography) used in this study are the [11C]-acetate and [18F]-FDG to estimate BAT oxidative metabolism and glucose metabolism, respectively. The perfusion of [6,6 D2]-glucose, [1,1,2,3,3-2H]-glycerol and [U-13C]-palmitate stable isotopes will also be performed in this study from time -150 min. to +300 min to examine the systemic appearance rate of glucose, glycerol and fatty acids, respectively. These studies will be almost identical (same perfusion of stable and radioactive tracers, same number of PET acquisitions) except for the drug which will be administered orally at time 0.
- Conditions
- Type 2 Diabetes
- Being tested
- Mirabegron, Bisoprolol Fumarate
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirabegronDrug
Also called Myrbetriq
Mirabegron: a single dose of 200 mg mirabegron (4 tablets of 50 mg)
Bisoprolol FumarateDrug
Also called Apo Bisoprolol
a single dose of 10 mg (2 tablets of 5 mg)
| Study group | Role | What they receive |
|---|---|---|
| Study A | Active comparator | Metabolic PET study with mirabegron Receives: Drug: Mirabegron |
| Study B | Experimental | Metabolic PET study with mirabegron and bisoprolol Receives: Drug: Mirabegron; Drug: Bisoprolol Fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in activation of Brown Adipose Tissue (BAT) (oxidative metabolism and blood flow)
Measured with 11C-acetate using dynamic PET/CT acquisition.
Measured: 30 minutes before and 210 minutes after drug administration
BAT glucose uptake
Assessed using i.v. injection of 18FDG with sequential dynamic PET/CT scanning
Measured: 240 minutes after drug administration
Secondary outcomes (6)
Whole-body glucose partitioning
Assessed using i.v. injection of 18FDG with static PET/CT scanning
Measured: 300 minutes after drug administration
Whole-body lipolysis
Systemic appearance rate of glycerol and fatty acid determined by perfusion of [1,1,2,3,3-2H]-glycerol, [U-13C]-palmitate tracers. and concentration of total NEFA, triglycerides, palmitate, oleate, linoleate, glycerol.
Measured: 150 minutes before and mean of time 180, 240 and 300 minutes after drug administration (steady state).
Hepatic Glucose production
Systemic appearance rate of glucose determined by perfusion of [6,6 D2]-glucose
Measured: 150 minutes before and mean of time 180, 240 and 300 minutes after drug administration (steady state).
Substrate utilisation
VO2 and VCO2 will be measured by indirect calorimetry to calculate carbohydrate and fatty acid oxidation rates.
Measured: 150 minutes before and mean of time 210 and 270 minutes after drug administration (steady state).
BAT lipolysis
Estimated by quantifying changes in tissue radiodensity with CT.
Measured: baseline and 300 minutes after drug administration
Changes in pancreatic and gut hormones
measured with ELISA and Milliplex.
Measured: 150 minutes before and mean of time 180, 240 and 300 minutes after drug administration (steady state).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2021
- Study start21 Jan 2021
- Primary completion4 Apr 2022
- Study completion4 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- Laval University
- Responsible party
- Principal investigator, Denis Blondin, Université de Sherbrooke
- Investigators
- Denis Blondin, Principal investigator, Université de Sherbrooke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04823442
- Sponsor's protocol ID
- 2021-3791
- Acronym
- GB9
- Status last verified
- Dec 2024
- First submitted
- 26 Mar 2021
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Dumont L, Caron A, Richard G, Croteau E, Fortin M, Frisch F, Phoenix S, Dubreuil S, Guerin B, Turcotte EE, Carpentier AC, Blondin DP. The effects of the beta1-adrenergic receptor antagonist bisoprolol administration on mirabegron-stimulated human brown adipose tissue thermogenesis. Acta Physiol (Oxf). 2024 May;240(5):e14127. doi: 10.1111/apha.14127. Epub 2024 Mar 19.
PubMed 38502056Chunchai T, Chinchapo T, Sripetchwandee J, Thonusin C, Chattipakorn N, Chattipakorn SC. Lipopolysaccharide exacerbates depressive-like behaviors in obese rats through complement C1q-mediated synaptic elimination by microglia. Acta Physiol (Oxf). 2024 May;240(5):e14130. doi: 10.1111/apha.14130. Epub 2024 Mar 10.
PubMed 38462756
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sympathomimetics and Sympatholytics in Type 2 Diabetes: Teaching Old Drugs New Tricks
- ClinicalTrials.gov ID
- NCT04823442
- Acronym / sponsor ID
- GB9 / 2021-3791
- Conditions
- Type 2 Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Université de SherbrookeUniversity, hospital or other
- Collaborators
- Laval University
- Study start
- 21 Jan 2021 (actual)
- Primary completion
- 4 Apr 2022 (actual)
- Study completion
- 4 Apr 2022 (actual)
- First posted
- 30 Mar 2021 (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.
Could sympathomimetics and sympatholytics drugs safe for the management of Type 2 Diabetes (T2D)? Based on recent evidence, we propose that pharmacological stimulation of Beta-3 adrenergic receptor (ADBR3) at higher doses of Mirabegron may be required to elicit changes in glycemia, but should be combined with Beta-1 adrenergic receptor (ADRB1) antagonists to suppress the unwanted effects on the cardiovascular system.
Together, several results establish a previously unappreciated cross-talk between Gs-coupled ADRB1 and ADRB3 in adipose tissue for the control of glucose homeostasis. Moreover, these data suggest that antagonizing ADRB1 may be a good way to significantly lower the dose of ADRB3 agonist required for glucose control.
Therefore, we believe that there are therapeutic opportunities in targeting adrenergic receptors for the treatment of T2D at least in young/middle aged people.
Detailed description
In brief, participants will take part in 2 metabolic studies (A and B) performed in random order and at an interval of 7 to 14 days. Each metabolic study will last 8.5 hours with a baseline period of 2.5 hours. Participants will ingest either 200 mg of the ADRB3 agonist mirabegron (Myrbetriq, Astellas Pharma Canada) alone (study A) or in combination with 10 mg of bisoprolol, an ADRB1-antagonist (study B), at time 0.
The radioactive PET tracers (PET: positron emission tomography) used in this study are the [11C]-acetate and [18F]-FDG to estimate BAT oxidative metabolism and glucose metabolism, respectively. The perfusion of [6,6 D2]-glucose, [1,1,2,3,3-2H]-glycerol and [U-13C]-palmitate stable isotopes will also be performed in this study from time -150 min. to +300 min to examine the systemic appearance rate of glucose, glycerol and fatty acids, respectively. These studies will be almost identical (same perfusion of stable and radioactive tracers, same number of PET acquisitions) except for the drug which will be administered orally at time 0.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study A | Active comparator | Drug: MirabegronMetabolic PET study with mirabegron |
| Study B | Experimental | Drug: Mirabegron, Drug: Bisoprolol FumarateMetabolic PET study with mirabegron and bisoprolol |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy subjects with normal glucose tolerance determined according to an oral glucose tolerance test;
- BMI ≤ 30 kg/m2.
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,betablockers or other drugs with effects on insulin resistance or lipid metabolism (exception for antihypertensive 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 |
|---|---|---|
| MirabegronAlso: MyrbetriqMirabegron: a single dose of 200 mg mirabegron (4 tablets of 50 mg) | Drug | Study A, Study B |
| Bisoprolol FumarateAlso: Apo Bisoprolola single dose of 10 mg (2 tablets of 5 mg) | Drug | Study B |
Primary outcome
Change in activation of Brown Adipose Tissue (BAT) (oxidative metabolism and blood flow)
Time frame: 30 minutes before and 210 minutes after drug administration
Measured with 11C-acetate using dynamic PET/CT acquisition.
BAT glucose uptake
Time frame: 240 minutes after drug administration
Assessed using i.v. injection of 18FDG with sequential dynamic PET/CT scanning
6 secondary outcomes
Whole-body glucose partitioning
Time frame: 300 minutes after drug administration
Whole-body lipolysis
Time frame: 150 minutes before and mean of time 180, 240 and 300 minutes after drug administration (steady state).
Hepatic Glucose production
Time frame: 150 minutes before and mean of time 180, 240 and 300 minutes after drug administration (steady state).
Substrate utilisation
Time frame: 150 minutes before and mean of time 210 and 270 minutes after drug administration (steady state).
BAT lipolysis
Time frame: baseline and 300 minutes after drug administration
Changes in pancreatic and gut hormones
Time frame: 150 minutes before and mean of time 180, 240 and 300 minutes after drug administration (steady state).
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 9 Dec 2024.
- Results publication: PubMed 38502056Dumont L, Caron A, Richard G, Croteau E, Fortin M, Frisch F, Phoenix S, Dubreuil S, Guerin B, Turcotte EE, Carpentier AC, Blondin DP. The effects of the beta1-adrenergic receptor antagonist bisoprolol administration on mirabegron-stimulated human brown adipose tissue thermogenesis. Acta Physiol (Oxf). 2024 May;240(5):e14127. doi: 10.1111/apha.14127. Epub 2024 Mar 19.
- Derived from this study: PubMed 38462756Chunchai T, Chinchapo T, Sripetchwandee J, Thonusin C, Chattipakorn N, Chattipakorn SC. Lipopolysaccharide exacerbates depressive-like behaviors in obese rats through complement C1q-mediated synaptic elimination by microglia. Acta Physiol (Oxf). 2024 May;240(5):e14130. doi: 10.1111/apha.14130. Epub 2024 Mar 10.
- publication of resultsLink provided by the sponsor.
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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.
Denis Blondin 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 Mirabegron and Bisoprolol Fumarate in people with Type 2 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 2 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 9 Dec 2024. 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?
Change in activation of Brown Adipose Tissue (BAT) (oxidative metabolism and blood flow) (time frame: 30 minutes before and 210 minutes after drug administration). The study lists 2 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 NCT04823442, which also lists 2 linked publications.
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 9 Dec 2024.