Brown Fat Activation Study

NCT02919176 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: 16-0642-F1VR01DK112282
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open lable, pilot study in which the investigator will research the effect of two FDA approved drugs, Mirabegron and Pioglitazone on fat tissue. Pioglitazone is drug approved by the FDA for the treatment of diabetes and Mirabegron is a drug that is approved by the FDA for the treatment of overactive bladder. These drugs are not approved by the FDA for the purposes being studied in this research. Therefore, the way in which the investigator intends to use them in this study are considered investigational.

Conditions

Obese; Metabolic Syndrome

Outcome Measures

Primary Outcomes (3)

• Change in beige adipose tissue

  Beige adipose tissue markers will be evaluated at baseline, and after treatment with mirabegron, pioglitazone, or both drugs

  baseline and after 10 weeks of treatment

• Change in brown adipose tissue

  Brown adipose tissue will be evaluated by PET-CT scan at baseline, and after treatment with mirabegron, pioglitazone, or both drugs

  baseline and after 10 weeks of treatment

• Change in insulin sensitivity

  Insulin sensitivity will be assessed at baseline and after treatment with mirabegron, pioglitazone, or both drugs, using a euglycemic clamp

  baseline and after 10 weeks of treatment

Secondary Outcomes (2)

• Change in body mass index

  baseline and after 10 weeks of treatment

• Change in glucose tolerance

  baseline and after 10 weeks of treatment

Study Arms (3)

Mirabegron

ACTIVE COMPARATOR

Mirabegron 50 mg/day

Drug: Mirabegron

Pioglitazone

ACTIVE COMPARATOR

Pioglitazone 30 mg/day

Drug: Pioglitazone

Mirabegron and Pioglitazone

EXPERIMENTAL

Combination of Mirabegron 50 mg/day and Pioglitazone 30 mg/day

Drug: Mirabegron and Pioglitazone

Interventions

Mirabegron DRUG

Mirabegron 50 mg/day

Also known as: MYRBETRIQ

Mirabegron

Pioglitazone DRUG

Pioglitazone 30 mg/day

Also known as: ACTOS

Pioglitazone

Mirabegron and Pioglitazone DRUG

Mirabegron 50 mg/day and Pioglitazone 30 mg/day

Also known as: MYRBETRIQ and ACTOS

Mirabegron and Pioglitazone

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• slightly abnormal blood sugar (A1C between 5.7 and 6.5 or impaired glucose tolerance)
• Metabolic Syndrome features (hypertension, abnormal lipids, abdominal obesity)
• Body Mass Index between 27-45
• Ambulatory

You may not qualify if:

• A history of heart disease
• Cancer or a history of cancer within the last 5 years
• Kidney disease
• Currently taking steroids or anticoagulants
• A chronic inflammatory condition such as rheumatoid arthritis or inflammatory bowel disease
• A body mass index (BMI) greater than 45
• Diabetes or the chronic use of any antidiabetic medications
• Uncontrolled blood pressure, urinary retention, overactive thyroid
• Significant swelling in hands, feet, face, arms.
• Currently taking β-blockers
• Daily use of NSAIDS or other anti-inflammatory drugs (eg. corticosteroids)
• Using low-dose aspirin (Participants will need to discontinue use for 7 days prior to the biopsies)
• Antiplatelet medication or blood thinners (examples: Aspirin, warfarin, Effient, Plavix)

Sponsors & Collaborators

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

Study Sites (1)

Center for Clinical and Translational Science

Lexington, Kentucky, 40536, United States

Location

Related Publications (3)

• Finlin BS, Memetimin H, Zhu B, Confides AL, Vekaria HJ, El Khouli RH, Johnson ZR, Westgate PM, Chen J, Morris AJ, Sullivan PG, Dupont-Versteegden EE, Kern PA. The beta3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans. J Clin Invest. 2020 May 1;130(5):2319-2331. doi: 10.1172/JCI134892.

  PMID: 31961829 RESULT

• Finlin BS, Memetimin H, Zhu B, Confides AL, Vekaria HJ, El Khouli RH, Johnson ZR, Westgate PM, Chen J, Morris AJ, Sullivan PG, Dupont-Versteegden EE, Kern PA. Pioglitazone does not synergize with mirabegron to increase beige fat or further improve glucose metabolism. JCI Insight. 2021 Mar 22;6(6):e143650. doi: 10.1172/jci.insight.143650.

  PMID: 33571166 DERIVED

• Finlin BS, Memetimin H, Confides AL, Kasza I, Zhu B, Vekaria HJ, Harfmann B, Jones KA, Johnson ZR, Westgate PM, Alexander CM, Sullivan PG, Dupont-Versteegden EE, Kern PA. Human adipose beiging in response to cold and mirabegron. JCI Insight. 2018 Aug 9;3(15):e121510. doi: 10.1172/jci.insight.121510. eCollection 2018 Aug 9.

  PMID: 30089732 DERIVED

MeSH Terms

Conditions

Obesity; Metabolic Syndrome

Interventions

mirabegron; Pioglitazone

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Philip Kern, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 22, 2016
• First Posted: September 29, 2016
• Study Start: September 1, 2016
• Primary Completion: February 4, 2019
• Study Completion: February 4, 2019
• Last Updated: February 7, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)