Activation of Brown Adipose Tissue Thermogenesis in Humans Using Formoterol Fumarate (GB10)
NCT ID: NCT05553184
Last Updated: 2023-11-28
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
NA
12 participants
INTERVENTIONAL
2022-07-05
2023-05-29
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Using acetate and fluorodeoxyglucose (FDG) positron emission tomography (PET) , It has been demonstrated that BAT thermogenesis is inducible by chronic cold exposure.
BAT activation through cold exposure is associated with improved glucose homeostasis and insulin sensitivity.
A pharmaceutical approach, which seemed to be very promising to stimulate the activation of BAT, was the use of a selective beta 3-adrenergic receptor agonist, mirabegron. Nevertheless, in a later study, It has been demonstrated that human BAT thermogenesis is under the control of beta-2, not beta-3, adrenergic receptor. The most selective beta-2 adrenergic receptor agonist approved for clinical use in Canada is formoterol fumarate, given in inhalation for the treatment of asthma (Oxeze®).
In summary, BAT contributes to cold-induced thermogenesis and is recruited by chronic cold exposure as well as by a growing number of food supplements and drugs. Intracellular triglyceride (TG) is the primary source of fuel for BAT thermogenesis under normal physiological conditions, as blocking intracellular TG lipolysis using nicotinic acid abolishes BAT thermogenesis. Beta-2 adrenergic stimulation is the pharmacological target to activate BAT thermogenesis in humans and may also lead to white adipose tissue lipolysis. Using a highly-selective beta-2 receptor agonist with and without administration of nicotinic acid would thus give the opportunity to quantify more precisely energy expenditure accounted by BAT thermogenesis and white adipose tissue metabolism in humans.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
1. during a 3-h cold exposure (Study A, control condition)
2. after inhalation of Formoterol with oral nicotinic acid (Study B)
3. after inhalation of Formoterol only (Study C).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
CROSSOVER
PREVENTION
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Acute Cold Exposure
3h-acute cold exposure.
Acute Cold Exposure
Participants will be fitted with a liquid-conditioned tube suit. The liquid-conditioned tube suit will be perfused with 18°C water using a temperature- and flow-controlled circulation bath from time 0 to 180 min.
Positron Emission Tomography (PET)
PET imaging using C11-palmitate (time 90), C11-acetate (time 120) and F18-Fluorodeoxyglucose (FDG) (time 150)
Indirect calorimetry
will be repeated every hour, for 20 minutes, using Vmax29n.
dual-energy x-ray absorptiometry (DEXA scan)
Whole body scan
Biopsy
After local anesthesia with 2% xylocaine without epinephrine, 100-200 mg of subcutaneous adipose tissue will be sampled by needle (14G) biopsy
iv lines
for stable tracer perfusion and blood sampling
Electromyogram (EMG)
Surface electrodes will be used to measure skeletal muscle activity and shivering intensity
Formoterol with nicotinic acid
Formoterol fumarate or Oxeze® Turbuhaler®: 48 µg (4 inhalations of 12 µg).
Nicotinic acid or Niacin: repeated doses of 150 MG every 30 minutes, for 3 hours.
Formoterol Fumarate 12 micrograms Inhalation Powder
At time 60 minutes, a total of 48 micrograms will be inhaled within 3 minutes: 4 inhalations of 12 micrograms of fumarate formoterol (Oxeze® Turbuhaler®).
Nicotinic Acid 50 MG Oral Tablet
a total dose of 1050 MG will be ingested. From time 0 to 180 minutes, doses of 150 MG will be repeated every 30 minutes.
Positron Emission Tomography (PET)
PET imaging using C11-palmitate (time 90), C11-acetate (time 120) and F18-Fluorodeoxyglucose (FDG) (time 150)
Indirect calorimetry
will be repeated every hour, for 20 minutes, using Vmax29n.
Biopsy
After local anesthesia with 2% xylocaine without epinephrine, 100-200 mg of subcutaneous adipose tissue will be sampled by needle (14G) biopsy
iv lines
for stable tracer perfusion and blood sampling
Formoterol without nicotinic acid
Formoterol fumarate or Oxeze® Turbuhaler®: 48 µg (4 inhalations of 12 µg).
Formoterol Fumarate 12 micrograms Inhalation Powder
At time 60 minutes, a total of 48 micrograms will be inhaled within 3 minutes: 4 inhalations of 12 micrograms of fumarate formoterol (Oxeze® Turbuhaler®).
Positron Emission Tomography (PET)
PET imaging using C11-palmitate (time 90), C11-acetate (time 120) and F18-Fluorodeoxyglucose (FDG) (time 150)
Indirect calorimetry
will be repeated every hour, for 20 minutes, using Vmax29n.
Biopsy
After local anesthesia with 2% xylocaine without epinephrine, 100-200 mg of subcutaneous adipose tissue will be sampled by needle (14G) biopsy
iv lines
for stable tracer perfusion and blood sampling
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Formoterol Fumarate 12 micrograms Inhalation Powder
At time 60 minutes, a total of 48 micrograms will be inhaled within 3 minutes: 4 inhalations of 12 micrograms of fumarate formoterol (Oxeze® Turbuhaler®).
Nicotinic Acid 50 MG Oral Tablet
a total dose of 1050 MG will be ingested. From time 0 to 180 minutes, doses of 150 MG will be repeated every 30 minutes.
Acute Cold Exposure
Participants will be fitted with a liquid-conditioned tube suit. The liquid-conditioned tube suit will be perfused with 18°C water using a temperature- and flow-controlled circulation bath from time 0 to 180 min.
Positron Emission Tomography (PET)
PET imaging using C11-palmitate (time 90), C11-acetate (time 120) and F18-Fluorodeoxyglucose (FDG) (time 150)
Indirect calorimetry
will be repeated every hour, for 20 minutes, using Vmax29n.
dual-energy x-ray absorptiometry (DEXA scan)
Whole body scan
Biopsy
After local anesthesia with 2% xylocaine without epinephrine, 100-200 mg of subcutaneous adipose tissue will be sampled by needle (14G) biopsy
iv lines
for stable tracer perfusion and blood sampling
Electromyogram (EMG)
Surface electrodes will be used to measure skeletal muscle activity and shivering intensity
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Exclusion Criteria
* The presence of any chronic medical condition requiring any pharmacological treatment;
* Previous intolerance or allergy to lactose, formoterol, nicotinic acid or local anesthetic agent;
* Any previous cardiac arrhythmia, long QT syndrome or hypokalemia;
* Chronic treatment with any medication other than contraceptives;
* Acute use of any drug other that acetaminophen or non-steroidal anti-inflammatory without decongestant or other stimulants;
* Smoking or consumption of more than 2 alcoholic beverages per day;
* Having participated to a research study with exposure to radiation in the last two years before the start of the study.
18 Years
45 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Université de Sherbrooke
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
André Carpentier
Tenure professor
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
André C. Carpentier, M.D.
Role: PRINCIPAL_INVESTIGATOR
Université de Sherbrooke
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Centre de recherche du CHUS
Sherbrooke, Quebec, Canada
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
GB10-2021-3873
Identifier Type: -
Identifier Source: org_study_id