NCT03049462

The Physiological Responses and Adaptation of Brown Adipose Tissue to Chronic Treatment With Beta3-Adrenergic Receptor Agonists

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · NIH
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Not accepted

Summary

Background: Brown adipose tissue (BAT) is a type of fat in the body. It may prevent weight gain, improve insulin sensitivity, and reduce fatty liver. Researchers want to see if BAT helps the body burn energy. Objective: To learn more about how BAT works to burn energy. Eligibility: People ages 18-40 with a body mass index between 18 and 40 Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Dietitian interview Participants will have an overnight baseline visit. This includes: Repeats of screening tests Exercise test Scans. For one scan, a radioactive substance is injected into the arm. FSIVGIT: An IV is inserted into veins in the right and left arms. Glucose and insulin are injected in one arm. Blood glucose and insulin levels are measured from the other. Metabolic suite: Participants stay 18-19 hours in a room that measures their metabolic rate. Monitors on the body measure heart rate, movement, and temperature. Optional fat biopsy: A small piece of tissue is removed with a needle. Participants will take 2-4 pills daily for 4 weeks. All women will take the drug mirabegron. Men will be randomly get either the drug or a placebo. All participants will have a visit after 2 weeks of the pills. They will repeat the screening tests. Participants will have an overnight visit 2 weeks later. They will repeat the baseline tests. Participants will keep food and medication diaries. Participants will have a follow-up visit 2 weeks after stopping the pills. This includes heart tests.

Detailed description

Study Description: This study is intended to address questions about human brown adipose tissue (BAT). Specifically, we plan to visualize BAT activity with acute cold exposure during drug naive and drug experienced visits. Thus, we will be studying changes in BAT activity from a chronic dosage of mirabegron. Objectives: Cohort 1: To measure changes in BAT metabolic activity in women seen after four weeks of daily treatment with the beta3-AR agonist mirabegron. Cohort 2: To measure changes in BAT metabolic activity in men seen after four weeks of daily treatment with 200 mg of the beta3-AR agonist mirabegron compared to placebo Cohort 3: To compare the changes in insulin sensitivity in each woman after four weeks of daily treatment with 100 mg of the beta3-AR agonist mirabegron with the changes in insulin sensitivity in each woman after four weeks of daily treatment with placebo Primary Endpoints: Cohort 1: The change in detectable cold exposure induced BAT metabolic activity in women, as visualized by F-FDG PET/CT. Cohort 2: The change in detectable cold exposure induced BAT metabolic activity, as visualized by 18F-FDG PET/CT Cohort 3: The change in glucose infusion rate, as measured by the hyperinsulinemic euglycemic clamp, in women after four weeks of daily treatment with 100 mg of the beta3-AR agonist mirabegron with the change in glucose infusion rate after four weeks of daily treatment with placebo Secondary Endpoints: 1. To identify changes in metabolic health arising from BAT activation and/or prolonged treatment with regular 100 mg (females) or 200mg (men) doses of mirabegron. 2. To determine if there is an interaction between (a) BMI and (b) age with respect to the capacity to increase BAT metabolic activity. 3. To describe the structural and physiological changes in the adipose tissue depots, including cell lineage, size, and inflammation. 4. To assess whether there are improvements in the liver, including reduced stiffness and quantity of hepatic fat.

Conditions

• Polycystic Ovary Syndrome

Interventions

Type	Name	Description
DRUG	Mirabegron	Women will take 100mg daily for 4 weeks. Men will take 200mg daily for 4 weeks. The medication is available in 50 mg tablets.
OTHER	B Complex Plus Vitamin C Tablets	Males will be randomized to take placebo versus active drug (mirabegron). Those taking placebo will take 4 tablets each day to mirror to active group (taking 4 tablets of 50 mg each).

Timeline

• Start date: 2017-03-13
• Primary completion: 2026-09-30
• Completion: 2026-09-30
• First posted: 2017-02-10
• Last updated: 2026-03-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study