Mechanisms for Activation of Beige Adipose Tissue in Humans
NCT ID: NCT04666636
Last Updated: 2025-12-17
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
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RECRUITING
PHASE2
65 participants
INTERVENTIONAL
2020-12-07
2026-12-01
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
PARALLEL
BASIC_SCIENCE
DOUBLE
Study Groups
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Placebo
Participants in the group will receive placebo.
Placebo
Participants will take one pill (placebo) daily for the first week and two pills daily for the remaining 15 weeks.
Mirabegron
Participants in this group will receive Mirabegron for 16 weeks.
Mirabegron
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.
Sub-Study: Mirabegron and the acute response to food
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.
Mirabegron 50 MG
Participants will take one pill (50mg Mirabegron) daily between visit 2 and visit 3
Sub-Study: Mirabegron dosing and Oral Glucose Tolerance Tests (Optional)
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.
Mirabegron 100 mg
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.
Interventions
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Placebo
Participants will take one pill (placebo) daily for the first week and two pills daily for the remaining 15 weeks.
Mirabegron
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 MG
Participants will take one pill (50mg Mirabegron) daily between visit 2 and visit 3
Mirabegron 100 mg
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* prediabetes (A1c 5.7-6.4)
* impaired fasting glucose or impaired glucose tolerance
Exclusion Criteria
* chronic use of anti-diabetic medication
* acute or chronic inflammatory condition
* unstable medical condition
* cancer
* renal insufficiency
* any contraindication for Mirabegron
* BMI \>45
35 Years
65 Years
ALL
Yes
Sponsors
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH
Philip Kern
OTHER
Responsible Party
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Philip Kern
Professor
Principal Investigators
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Philip Kern, MD
Role: PRINCIPAL_INVESTIGATOR
University of Kentucky
Locations
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University of Kentucky
Lexington, Kentucky, United States
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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60821
Identifier Type: -
Identifier Source: org_study_id