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Type 2 DiabetesGB10NCT05553184

Activation of Brown Adipose Tissue Thermogenesis in Humans Using Formoterol Fumarate (GB10)

A study testing Formoterol Fumarate 12 micrograms Inhalation Powder, Nicotinic Acid 50 MG Oral Tablet and Acute Cold Exposure in people with Type 2 Diabetes and Obesity, run by Université de Sherbrooke at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

One emerging, highly modifiable homeostatic mechanism for energy expenditure in humans is brown adipose tissue (BAT) thermogenesis. BAT is currently considered a prime target for the treatment of obesity and Type 2 diabetes (T2D). Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Type 2 Diabetes, Obesity
What is being tested?
Formoterol Fumarate 12 micrograms Inhalation Powder, Nicotinic Acid 50 MG Oral Tablet and Acute Cold Exposure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteCanada
Study dates
5 Jul 2022to 29 May 2023
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 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • BMI of 18 to 30 kg/m2.

Who cannot join

  • Change in weight of more than 2 kg over the past 3 months or recent changes in lifestyle;
  • 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Centre de recherche du CHUS

    Sherbrooke, Quebec, J1H 5N4

Other trials in Canada

About this study

Official title: Activation of Brown Adipose Tissue Thermogenesis in Humans Using Formoterol Fumarate, a Beta-2 Adrenergic Receptor Agonist

One emerging, highly modifiable homeostatic mechanism for energy expenditure in humans is brown adipose tissue (BAT) thermogenesis. BAT is currently considered a prime target for the treatment of obesity and Type 2 diabetes (T2D).

Using acetate and fluorodeoxyglucose (FDG) positron emission tomography (PET) , It has been demonstrated that BAT thermogenesis is inducible by chronic cold exposure.

Read more

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.

Read the detailed description

Each participant will undergo three metabolic sessions with PET imaging using [11C]-palmitate, [11C]-acetate and [18F]-FDG:

  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).
Being tested
Formoterol Fumarate 12 micrograms Inhalation Powder, Nicotinic Acid 50 MG Oral Tablet, Acute Cold Exposure, Positron Emission Tomography (PET), Indirect calorimetry
Keywords
Brown adipose tissue, formoterol fumarate, Thermogenesis
Medical subject headings
Diabetes Mellitus, Type 2, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Formoterol Fumarate 12 micrograms Inhalation PowderDrug

    Also called Oxeze Turbuhaler

    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 TabletDrug

    Also called Niacin 50 MG

    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 ExposureOther

    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)Diagnostic test

    PET imaging using C11-palmitate (time 90), C11-acetate (time 120) and F18-Fluorodeoxyglucose (FDG) (time 150)

  • Indirect calorimetryDiagnostic test

    will be repeated every hour, for 20 minutes, using Vmax29n.

  • dual-energy x-ray absorptiometry (DEXA scan)Diagnostic test

    Whole body scan

  • BiopsyProcedure or surgery

    After local anesthesia with 2% xylocaine without epinephrine, 100-200 mg of subcutaneous adipose tissue will be sampled by needle (14G) biopsy

  • iv linesProcedure or surgery

    for stable tracer perfusion and blood sampling

  • Electromyogram (EMG)Procedure or surgery

    Surface electrodes will be used to measure skeletal muscle activity and shivering intensity

Study groups in NCT05553184
Study groupRoleWhat they receive
Acute Cold ExposureActive comparator3h-acute cold exposure.
Receives: Other: Acute Cold Exposure; Diagnostic Test: Positron Emission Tomography (PET); Diagnostic Test: Indirect calorimetry; Diagnostic Test: dual-energy x-ray absorptiometry (DEXA scan); Procedure: Biopsy; Procedure: iv lines; Procedure: Electromyogram (EMG)
Formoterol with nicotinic acidExperimentalFormoterol 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.
Receives: Drug: Formoterol Fumarate 12 micrograms Inhalation Powder; Drug: Nicotinic Acid 50 MG Oral Tablet; Diagnostic Test: Positron Emission Tomography (PET); Diagnostic Test: Indirect calorimetry; Procedure: Biopsy; Procedure: iv lines
Formoterol without nicotinic acidExperimentalFormoterol fumarate or Oxeze® Turbuhaler®: 48 µg (4 inhalations of 12 µg).
Receives: Drug: Formoterol Fumarate 12 micrograms Inhalation Powder; Diagnostic Test: Positron Emission Tomography (PET); Diagnostic Test: Indirect calorimetry; Procedure: Biopsy; Procedure: iv lines

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Brown Adipose Tissue thermogenesis (formoterol induced, cold-induced and effect of nicotinic acid)

    determined using [11C]-acetate PET

    Measured: measured 60 minutes before and 90 minutes after cold exposure (A) and 30 minutes after inhalation of Fumarate Formoterol (B and C)

Secondary outcomes (10)

  1. Brown Adipose Tissue (BAT) glucose uptake

    determined using [18F]-FDG dynamic PET acquisition

    Measured: measured 150 minutes after the start of acute cold exposure (A), and 90 minutes after inhalation of Fumarate Formoterol (B and C)

  2. Brown Adipose Tissue nonesterified fatty acid (NEFA) metabolism (uptake, oxidation, esterification and release rates)

    determined using [11C]-palmitate PET method

    Measured: measured 120 minutes after the start of acute cold exposure (A), and 60 minutes after inhalation of Fumarate Formoterol (B and C)

  3. Change in systemic plasma NEFA turnover.

    Determined using continuous infusion of labelled palmitate from time -60 to 180.

    Measured: measured at baseline and every 60 minutes after the start of acute cold exposure (A) and every 60 minutes after inhalation of fumarate formoterol (B and C), for 4 hours

  4. Change in systemic plasma glycerol turnover.

    Determined using continuous infusion of [1,1,2,3,3-D2]-glycerol from time -60 to 180 .

    Measured: measured at baseline and every hour after the start of acute cold exposure (A) and every hour after inhalation of fumarate formoterol (B and C), for 4 hours.

  5. Change in systemic plasma glucose turnover.

    Determined using continuous infusion of [6,6 D2]-glucose from time -150 to 180 .

    Measured: measured at baseline and every hour after the start of acute cold exposure (A) and every hour after inhalation of fumarate formoterol (B and C), for 5.50 hours

  6. BAT triglyceride content

    Determined using the CT radio-density method

    Measured: measured 180 minutes after the start of cold exposure (A) and 90 minutes after inhalation of fumarate formoterol (B and C)

  7. Change in whole-body energy expenditure

    Determined using indirect calorimetry

    Measured: measured at baseline and every hour after the start of acute cold exposure (A) and every hour after inhalation of fumarate formoterol (B and C), for 4 hours

  8. Muscle shivering activity

    Determined using the surface electromyogram (EMG)

    Measured: measured at baseline and every hour after the start of acute cold exposure (A) and every hour after inhalation of fumarate formoterol (B and C), for 4 hours

  9. Change in insulin sensitivity

    Determined by measuring circulating glucose, NEFA, insulin and C-peptide

    Measured: measured at baseline and every 60 minutes after the start of acute cold exposure (A) and every 60 minutes after inhalation of fumarate formoterol (B and C), for 4 hours.

  10. Protein expression of subcutaneous abdominal white adipose tissue

    Using biopsy

    Measured: measured at baseline and 180 minutes after the start of the cold exposure (study A) and 120 minutes after inhalation of fumarate formoterol (study B and C)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2022
  2. Study start5 Jul 2022
  3. Primary completion29 May 2023
  4. Study completion29 May 2023

Resources

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
Prevention
Allocation
Randomised
Intervention model
Crossover
Model description
The protocol will be carried out as a within-subject, randomized, cross-over study in which each subject will serve as his/her own control
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05553184
Sponsor's protocol ID
GB10-2021-3873
Acronym
GB10
Status last verified
Nov 2023
First submitted
25 Aug 2022
Last updated
28 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A study testing Formoterol Fumarate 12 micrograms Inhalation Powder, Nicotinic Acid 50 MG Oral Tablet and Acute Cold Exposure in people with Type 2 Diabetes and Obesity, 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 8 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 28 Nov 2023. 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 Brown Adipose Tissue thermogenesis (formoterol induced, cold-induced and effect of nicotinic acid) (time frame: measured 60 minutes before and 90 minutes after cold exposure (A) and 30 minutes after inhalation of Fumarate Formoterol (B and C)). 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 NCT05553184.

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 28 Nov 2023.

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