Mechanisms for Activation of Beige Adipose Tissue in Humans

NCT04666636 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 60821R01DK124626
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

PreDiabetes

Keywords

beige; adipose; glucose; fat; BAT; diabetes; metabolism; DEXA

Outcome Measures

Primary Outcomes (9)

• Change in Glucose Tolerance

  The standard oral glucose tolerance test (OGTT) using 75g glucose will be used to assess tolerance.

  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).

  16 weeks (at baseline and at 16 weeks)

• Change in Resting Metabolic Rate

  Resting Metabolic Rate (RMR) will be measured using indirect calorimetry.

  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).

  16 weeks (at baseline and at 16 weeks)

• Change in Peripheral Insulin Sensitivity

  Peripheral insulin sensitivity will be measured with a euglycemic clamp.

  16 weeks (at baseline and at 16 weeks)

• Change in Insulin Secretion

  Insulin secretion will be measured with a euglycemic clamp.

  16 weeks (at baseline and at 16 weeks)

• Change in glycohemoglobin

  Hemoglobin A1c (HbA1C) will be measured from blood samples.

  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.

  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.

  Baseline, week 1, week 2

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Participants in the group will receive placebo.

Drug: Placebo

Mirabegron

EXPERIMENTAL

Participants in this group will receive Mirabegron for 16 weeks.

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.

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.

Drug: Mirabegron 100 mg

Interventions

Placebo DRUG

Participants will take one pill (placebo) daily for the first week and two pills daily for the remaining 15 weeks.

Placebo

Mirabegron DRUG

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.

Also known as: Myrbetriq

Mirabegron

Mirabegron 50 MG DRUG

Participants will take one pill (50mg Mirabegron) daily between visit 2 and visit 3

Also known as: Myrbetriq

Sub-Study: Mirabegron and the acute response to food

Mirabegron 100 mg DRUG

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.

Also known as: Myrbetriq

Sub-Study: Mirabegron dosing and Oral Glucose Tolerance Tests (Optional)

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI 27-45
• prediabetes (A1c 5.7-6.4)
• impaired fasting glucose or impaired glucose tolerance

You may not qualify if:

• diabetes
• chronic use of anti-diabetic medication
• acute or chronic inflammatory condition
• unstable medical condition
• cancer
• renal insufficiency
• any contraindication for Mirabegron
• BMI \>45

Sponsors & Collaborators

• Philip Kern: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

RECRUITING

MeSH Terms

Conditions

Prediabetic State; Platelet Glycoprotein IV Deficiency; Diabetes Mellitus

Interventions

mirabegron

Condition Hierarchy (Ancestors)

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

Study Officials

• Philip Kern, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zach Leicht

CONTACT

859-218-1397; zachary.leicht@uky.edu

Philip Kern, MD

CONTACT

859-218-1394; pake222@uky.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 14, 2020
• Study Start: December 7, 2020
• Primary Completion (Estimated): June 25, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 3, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)