PreDiabetesPhase 2NCT04666636
Mechanisms for Activation of Beige Adipose Tissue in Humans
A Phase 2 study testing Mirabegron, Mirabegron 50 MG and Mirabegron 100 mg in people with PreDiabetes, run by Philip Kern at 1 site in United States.
Trial summary
Mirabegron (Myrbetriq®, Astellas) is a highly specific and well-tolerated ß3 agonist marketed for overactive bladder. This trial will assess the effects of mirabegron on glucose tolerance and adipose tissue in prediabetic patients Read more about this study
- Who is it for?
- Ages 35 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- PreDiabetes
- What is being tested?
- Mirabegron, Mirabegron 50 MG and Mirabegron 100 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2020to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 35 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- BMI 27-45
- prediabetes (A1c 5.7-6.4)
- impaired fasting glucose or impaired glucose tolerance
Who cannot join
- diabetes
- chronic use of anti-diabetic medication
- acute or chronic inflammatory condition
- unstable medical condition
- cancer
- renal insufficiency
- any contraindication for Mirabegron
- BMI >45
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Kentucky
Lexington, Kentucky, 40536
Zach Leicht, 859-218-1397, zachary.leicht@uky.edu
Philip Kern, MD
About this study
Mirabegron (Myrbetriq®, Astellas) is a highly specific and well-tolerated ß3 agonist marketed for overactive bladder. This trial will assess the effects of mirabegron on glucose tolerance and adipose tissue in prediabetic patients
Read the detailed description
Among the many survival adaptations developed by mammals is a defense against the cold and hypothermia; one of these adaptations is the ability to uncouple oxidative phosphorylation and generate heat, rather than adenosine triphosphate (ATP), from lipid substrate in specialized tissues, and there has been much interest in exploiting this inefficient metabolism for the treatment of obesity and insulin resistance. Brown adipose tissue (BAT) protects against obesity in mice, and studies have documented cold-induced BAT in humans using positron emission tomography (PET-CT) scanning. Additional studies have demonstrated that white adipose tissue (WAT) can upregulate its thermogenic capacity and become "beige", and this beiging of SC WAT likely provides an additional defense against the cold.
Brown and beige fat can be activated by cold temperatures, or through catecholamines. The catecholamines epinephrine and norepinephrine have undesirable side effects. However, adipocytes are among the few cells that contain ß3 adrenergic receptors (ß3AR), whereas the heart is dominated by ß1 and ß2 receptors. Therefore, a drug that could target the ß3AR could activate brown/beige fat without cardiovascular side effects. Recently, there have been human studies performed and obese human subjects participants were treated with the ß3AR agonist mirabegron. This resulted in improved glucose homeostasis by increasing insulin sensitivity and insulin secretion. It was also found that mirabegron treatment of obese adults did not increase BAT or induce weight loss, but instead induced beige fat, along with increased insulin sensitivity, which was accompanied by an increase in type I fibers in skeletal muscle. Mirabegron treatment stimulated subcutaneous (SC) WAT beiging, lipolysis, and remodeling. However, unlike WAT, insulin-producing ß-cells and muscle do not express the ß3AR; therefore, it is thought that the beneficial effects of mirabegron treatment occurred by an indirect mechanism.
Currently, mirabegron (Myrbetriq®, Astellas) is a highly specific and well-tolerated ß3 agonist marketed for overactive bladder. It is hypothesized that mirabegron treatment of prediabetic subjects will improve glucose homeostasis through improved insulin sensitivity and ß-cell function, in addition to other changes in adipose tissue. Additionally, mirabegron treatment may change the plasma composition of proteins, lipids, metabolites, short-chain fatty acids, or exosomal miRNAs that are known to affect peripheral tissue function.
This trial will quantify the effects of the ß3 agonist mirabegron on glucose metabolism and adipose tissue in a placebo-controlled trial and determine some of the mechanistic underpinnings of these effects.
- Conditions
- PreDiabetes
- Being tested
- Placebo, Mirabegron, Mirabegron 50 MG, Mirabegron 100 mg
- Keywords
- beige, adipose, glucose, fat, BAT, diabetes, metabolism, DEXA
- Medical subject headings
- Prediabetic State, Platelet Glycoprotein IV Deficiency, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Participants will take one pill (placebo) daily for the first week and two pills daily for the remaining 15 weeks.
MirabegronDrug
Also called Myrbetriq
Participants will take one pill (50mg Mirabegron) daily for the first week. For week two, participants will take two pills (50mg and 25mg Mirabegron). Unless there are side effects, for the remaining 14 weeks participants will take two pills (50mg each) daily.
Mirabegron 50 MGDrug
Also called Myrbetriq
Participants will take one pill (50mg Mirabegron) daily between visit 2 and visit 3
Mirabegron 100 mgDrug
Also called Myrbetriq
participants will be given 6 weeks of mirabegron (25 mg) and will take 1 pill once per day for 4-6 weeks. Next participants will be given 6 weeks of mirabegron (50 mg) and take 1 pill once per day for 4-6 weeks. Last participants will be given 6 weeks of mirabegron (100 mg) and take 1 pill once per day for 4-6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants in the group will receive placebo. Receives: Drug: Placebo |
| Mirabegron | Experimental | Participants in this group will receive Mirabegron for 16 weeks. Receives: Drug: Mirabegron |
| Sub-Study: Mirabegron and the acute response to food | Experimental | This sub-study will involve the recruiting of the same subjects who are eligible for this study as described above. Subjects will report to the CCTS fasting on 3 separate days. On each visit, the subject will have 5 blood draws and each blood draw will be about 8 ml, for a total of 40 ml of blood at each visit. Visit 1 will involve the participant consuming a standardized meal. At visit 2, participants will take 50mg of Mirabegron. And visit 3 will involve the participant consuming the same meal as visit 1 and also taking 50 mg of mirabegron. Receives: Drug: Mirabegron 50 MG |
| Sub-Study: Mirabegron dosing and Oral Glucose Tolerance Tests (Optional) | Experimental | Studies have found that larger doses of mirabegron do not elicit the same improvements in insulin sensitivity. Therefore, we aim to perform a dose-response study to gain an improved understanding of mirabegron dosing and changes in insulin sensitivity.
This sub-study will have 4 total visits. visit 1 is a baseline oral glucose tolerance test. At the end of visit 1, participants will be given 6 weeks of mirabegron (25 mg) and will take 1 pill once per day for 4-6 weeks leading up to visit 2. Visit 2 will also be a standard oral glucose tolerance test. At the end of visit 2, participants will be given 6 weeks of mirabegron (50 mg) and take 1 pill once per day for 4-6 weeks leading up to visit 3. Visit 3 will also be a standard oral glucose tolerance test. At the end of visit 3, participants will be given 6 weeks of mirabegron (10 mg) and take 1 pill once per day for 4-6 weeks. Visit 4 will be the final visit and will also be a standard oral glucose tolerance test. Receives: Drug: Mirabegron 100 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glucose Tolerance
The standard oral glucose tolerance test (OGTT) using 75g glucose will be used to assess tolerance.
Measured: 16 weeks (at baseline and at 16 weeks)
Change in Body Composition
Body composition (percent body fat) will be measured using dual-energy X-ray absorptiometry (DEXA).
Measured: 16 weeks (at baseline and at 16 weeks)
Change in Resting Metabolic Rate
Resting Metabolic Rate (RMR) will be measured using indirect calorimetry.
Measured: 16 weeks (at baseline and at 16 weeks)
Change in Brown Adipose Tissue Activity
Brown adipose tissue (BAT) activity will be measured using water-vest cold stimulation combined with positron emission tomography (PET-CT).
Measured: 16 weeks (at baseline and at 16 weeks)
Change in Peripheral Insulin Sensitivity
Peripheral insulin sensitivity will be measured with a euglycemic clamp.
Measured: 16 weeks (at baseline and at 16 weeks)
Change in Insulin Secretion
Insulin secretion will be measured with a euglycemic clamp.
Measured: 16 weeks (at baseline and at 16 weeks)
Change in glycohemoglobin
Hemoglobin A1c (HbA1C) will be measured from blood samples.
Measured: 16 weeks (at baseline and at 16 weeks)
Change in Matsuda Index for Dosing Sub Study
Comparison of change in Matsuda Index as determined by 2-h oral glucose tolerance test (OGTT). During OGTT, response to oral 75g glucose intake is determined by measuring insulin and glucose in timed samples obtained at 0, 30, 60, 90 and 120 min. Increase in scores reflect improvement in whole body insulin sensitivity.
Measured: Baseline, week 6, week 12, week 18
Change in bile acids/blood proteins
FGF-19 and total bile acids will be analyzed and compared across the different conditions. Plasma bile acid concentration (ng/mL) will be measured and compared across the different doses of study drug.
Measured: Baseline, week 1, week 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2020
- Study start7 Dec 2020
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PreDiabetesStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Philip Kern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Philip Kern, University of Kentucky
- Investigators
- Philip Kern, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04666636
- Sponsor's protocol ID
- 60821
- Other IDs
- R01DK124626
- Status last verified
- Oct 2025
- First submitted
- 7 Dec 2020
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms for Activation of Beige Adipose Tissue in Humans
- ClinicalTrials.gov ID
- NCT04666636
- Acronym / sponsor ID
- 60821
- Conditions
- PreDiabetes
- Keywords
- beige, adipose, glucose, fat, BAT, diabetes, metabolism, DEXA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Philip KernUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 7 Dec 2020 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 14 Dec 2020 (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.
Mirabegron (Myrbetriq®, Astellas) is a highly specific and well-tolerated ß3 agonist marketed for overactive bladder. This trial will assess the effects of mirabegron on glucose tolerance and adipose tissue in prediabetic patients
Detailed description
Among the many survival adaptations developed by mammals is a defense against the cold and hypothermia; one of these adaptations is the ability to uncouple oxidative phosphorylation and generate heat, rather than adenosine triphosphate (ATP), from lipid substrate in specialized tissues, and there has been much interest in exploiting this inefficient metabolism for the treatment of obesity and insulin resistance. Brown adipose tissue (BAT) protects against obesity in mice, and studies have documented cold-induced BAT in humans using positron emission tomography (PET-CT) scanning. Additional studies have demonstrated that white adipose tissue (WAT) can upregulate its thermogenic capacity and become "beige", and this beiging of SC WAT likely provides an additional defense against the cold.
Brown and beige fat can be activated by cold temperatures, or through catecholamines. The catecholamines epinephrine and norepinephrine have undesirable side effects. However, adipocytes are among the few cells that contain ß3 adrenergic receptors (ß3AR), whereas the heart is dominated by ß1 and ß2 receptors. Therefore, a drug that could target the ß3AR could activate brown/beige fat without cardiovascular side effects. Recently, there have been human studies performed and obese human subjects participants were treated with the ß3AR agonist mirabegron. This resulted in improved glucose homeostasis by increasing insulin sensitivity and insulin secretion. It was also found that mirabegron treatment of obese adults did not increase BAT or induce weight loss, but instead induced beige fat, along with increased insulin sensitivity, which was accompanied by an increase in type I fibers in skeletal muscle. Mirabegron treatment stimulated subcutaneous (SC) WAT beiging, lipolysis, and remodeling. However, unlike WAT, insulin-producing ß-cells and muscle do not express the ß3AR; therefore, it is thought that the beneficial effects of mirabegron treatment occurred by an indirect mechanism.
Currently, mirabegron (Myrbetriq®, Astellas) is a highly specific and well-tolerated ß3 agonist marketed for overactive bladder. It is hypothesized that mirabegron treatment of prediabetic subjects will improve glucose homeostasis through improved insulin sensitivity and ß-cell function, in addition to other changes in adipose tissue. Additionally, mirabegron treatment may change the plasma composition of proteins, lipids, metabolites, short-chain fatty acids, or exosomal miRNAs that are known to affect peripheral tissue function.
This trial will quantify the effects of the ß3 agonist mirabegron on glucose metabolism and adipose tissue in a placebo-controlled trial and determine some of the mechanistic underpinnings of these effects.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants in the group will receive placebo. |
| Mirabegron | Experimental | Drug: MirabegronParticipants in this group will receive Mirabegron for 16 weeks. |
| Sub-Study: Mirabegron and the acute response to food | Experimental | Drug: Mirabegron 50 MGThis sub-study will involve the recruiting of the same subjects who are eligible for this study as described above. Subjects will report to the CCTS fasting on 3 separate days. On each visit, the subject will have 5 blood draws and each blood draw will be about 8 ml, for a total of 40 ml of blood at each visit. Visit 1 will involve the participant consuming a standardized meal. At visit 2, participants will take 50mg of Mirabegron. And visit 3 will involve the participant consuming the same meal as visit 1 and also taking 50 mg of mirabegron. |
| Sub-Study: Mirabegron dosing and Oral Glucose Tolerance Tests (Optional) | Experimental | Drug: Mirabegron 100 mgStudies have found that larger doses of mirabegron do not elicit the same improvements in insulin sensitivity. Therefore, we aim to perform a dose-response study to gain an improved understanding of mirabegron dosing and changes in insulin sensitivity. This sub-study will have 4 total visits. visit 1 is a baseline oral glucose tolerance test. At the end of visit 1, participants will be given 6 weeks of mirabegron (25 mg) and will take 1 pill once per day for 4-6 weeks leading up to visit 2. Visit 2 will also be a standard oral glucose tolerance test. At the end of visit 2, participants will be given 6 weeks of mirabegron (50 mg) and take 1 pill once per day for 4-6 weeks leading up to visit 3. Visit 3 will also be a standard oral glucose tolerance test. At the end of visit 3, participants will be given 6 weeks of mirabegron (10 mg) and take 1 pill once per day for 4-6 weeks. Visit 4 will be the final visit and will also be a standard oral glucose tolerance test. |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- BMI 27-45
- prediabetes (A1c 5.7-6.4)
- impaired fasting glucose or impaired glucose tolerance
Key exclusion criteria (8 listed)
- diabetes
- chronic use of anti-diabetic medication
- acute or chronic inflammatory condition
- unstable medical condition
- cancer
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 |
|---|---|---|
| PlaceboParticipants will take one pill (placebo) daily for the first week and two pills daily for the remaining 15 weeks. | Drug | Placebo |
| MirabegronAlso: MyrbetriqParticipants will take one pill (50mg Mirabegron) daily for the first week. For week two, participants will take two pills (50mg and 25mg Mirabegron). Unless there are side effects, for the remaining 14 weeks participants will take two pills (50mg each) daily. | Drug | Mirabegron |
| Mirabegron 50 MGAlso: MyrbetriqParticipants will take one pill (50mg Mirabegron) daily between visit 2 and visit 3 | Drug | Sub-Study: Mirabegron and the acute response to food |
| Mirabegron 100 mgAlso: Myrbetriqparticipants will be given 6 weeks of mirabegron (25 mg) and will take 1 pill once per day for 4-6 weeks. Next participants will be given 6 weeks of mirabegron (50 mg) and take 1 pill once per day for 4-6 weeks. Last participants will be given 6 weeks of mirabegron (100 mg) and take 1 pill once per day for 4-6 weeks. | Drug | Sub-Study: Mirabegron dosing and Oral Glucose Tolerance Tests (Optional) |
Primary outcome
Change in Glucose Tolerance
Time frame: 16 weeks (at baseline and at 16 weeks)
The standard oral glucose tolerance test (OGTT) using 75g glucose will be used to assess tolerance.
Change in Body Composition
Time frame: 16 weeks (at baseline and at 16 weeks)
Body composition (percent body fat) will be measured using dual-energy X-ray absorptiometry (DEXA).
Change in Resting Metabolic Rate
Time frame: 16 weeks (at baseline and at 16 weeks)
Resting Metabolic Rate (RMR) will be measured using indirect calorimetry.
Change in Brown Adipose Tissue Activity
Time frame: 16 weeks (at baseline and at 16 weeks)
Brown adipose tissue (BAT) activity will be measured using water-vest cold stimulation combined with positron emission tomography (PET-CT).
Change in Peripheral Insulin Sensitivity
Time frame: 16 weeks (at baseline and at 16 weeks)
Peripheral insulin sensitivity will be measured with a euglycemic clamp.
Change in Insulin Secretion
Time frame: 16 weeks (at baseline and at 16 weeks)
Insulin secretion will be measured with a euglycemic clamp.
Change in glycohemoglobin
Time frame: 16 weeks (at baseline and at 16 weeks)
Hemoglobin A1c (HbA1C) will be measured from blood samples.
Change in Matsuda Index for Dosing Sub Study
Time frame: Baseline, week 6, week 12, week 18
Comparison of change in Matsuda Index as determined by 2-h oral glucose tolerance test (OGTT). During OGTT, response to oral 75g glucose intake is determined by measuring insulin and glucose in timed samples obtained at 0, 30, 60, 90 and 120 min. Increase in scores reflect improvement in whole body insulin sensitivity.
Change in bile acids/blood proteins
Time frame: Baseline, week 1, week 2
FGF-19 and total bile acids will be analyzed and compared across the different conditions. Plasma bile acid concentration (ng/mL) will be measured and compared across the different doses of study drug.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- 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.
Philip Kern, MD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mirabegron, Mirabegron 50 MG and Mirabegron 100 mg in people with PreDiabetes, run by Philip Kern at 1 site in United States.
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 3 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: looking for participants now, as of the sponsor's last update on 7 Jul 2026. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zach Leicht (859-218-1397, zachary.leicht@uky.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Glucose Tolerance (time frame: 16 weeks (at baseline and at 16 weeks)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Jul 2026.