Activation of Brown Adipose Tissue Metabolism Using Mirabegron

NCT04823442 | Completed

• 1 other identifier: 2021-3791
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (2)

• Change in activation of Brown Adipose Tissue (BAT) (oxidative metabolism and blood flow)

  Measured with 11C-acetate using dynamic PET/CT acquisition.

  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

  240 minutes after drug administration

Secondary Outcomes (6)

• Whole-body glucose partitioning

  300 minutes after drug administration

• Whole-body lipolysis

  150 minutes before and mean of time 180, 240 and 300 minutes after drug administration (steady state).

• Hepatic Glucose production

  150 minutes before and mean of time 180, 240 and 300 minutes after drug administration (steady state).

• Substrate utilisation

  150 minutes before and mean of time 210 and 270 minutes after drug administration (steady state).

• BAT lipolysis

  baseline and 300 minutes after drug administration

Study Arms (2)

Study A

ACTIVE COMPARATOR

Metabolic PET study with mirabegron

Drug: Mirabegron

Study B

EXPERIMENTAL

Metabolic PET study with mirabegron and bisoprolol

Drug: Mirabegron; Drug: Bisoprolol Fumarate

Interventions

Mirabegron DRUG

Mirabegron: a single dose of 200 mg mirabegron (4 tablets of 50 mg)

Also known as: Myrbetriq

Study A; Study B

Bisoprolol Fumarate DRUG

a single dose of 10 mg (2 tablets of 5 mg)

Also known as: Apo Bisoprolol

Study B

Eligibility Criteria

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

You may qualify if:

• Healthy subjects with normal glucose tolerance determined according to an oral glucose tolerance test;
• BMI ≤ 30 kg/m2.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Laval University: collaborator

Study Sites (1)

Centre de recherche du CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Related Publications (2)

• 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.

  PMID: 38502056 RESULT

• Chunchai 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.

  PMID: 38462756 DERIVED

Related Links

• publication of results

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

mirabegron; Bisoprolol

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Denis Blondin

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assisant professor

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: March 30, 2021
• Study Start: January 21, 2021
• Primary Completion: April 4, 2022
• Study Completion: April 4, 2022
• Last Updated: December 9, 2024

Record last verified: 2024-12

Locations

CA (1)