Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate

Summary

Background:

\- Changes in how a person's body burns energy or calories can affect their weight over time. The lowest level of energy the body needs to function is called basal metabolic rate. In the cold, we burn extra energy, even before we start to shiver. This is called non-shivering thermogenesis and it occurs in different types of tissue such as muscle and fat. Researchers want to learn more about this type of energy burning and how it is regulated. They hope this will help treat obesity in the future.

Objectives:

* Sub-study 1: to better understand how non-shivering thermogenesis works.
* Sub-study 2: to measure the effects of anti-obesity drugs on basal metabolic rate.
* Sub-study 3: to better understand the effects of mirabegron, a beta-3 adrenergic receptor agonist, on brown fat activity.

Eligibility:

\- Healthy, lean adult males ages 18 to 35.

Design:

* Participants will be screened with medical history, physical exam, blood test, and EKG.
* For sub-studies 1 and 2:

* Participants will receive one X-ray scan.
* Each day, all participants will:
* Have height and weight measured, and have urine collected.
* Spend 4 hours in a temperature-controlled room with furniture, toilet area, phone, and computer. They will wear small non-invasive devices to monitor activity, heart rate, temperature, and shivering.
* Walk for 30 minutes.
* For sub-study 3:

* Participants will receive one DXA scan and up to 4 PET/CT scans and 4 MRIs
* Each stay, all participants will:
* Have height and weight measured, and have urine collected.
* Spend 6 hours in a temperature-controlled room with furniture, toilet area, phone, and computer. They will wear small non-invasive devices to monitor activity, heart rate, temperature, and shivering.
* Participants will be compensated for their time and participation at the end of the study

Conditions

• Healthy Volunteers

Interventions

DRUG

Propranolol

Propanolol 160mg, oral, by mouth (Cohort 1 only)

DRUG

Pindolol

Pindolol 20mg, oral, by mouth (Cohort 1 only)

DRUG

Dantrolene

Dantrolene 100mg, oral, by mouth (Cohort 1 only)

DRUG

Magnesium Sulfate

Magnesium Sulfate, infusion, 50 mg/kg bolus followed by maintenance infusion at 2g/h (Cohort 1 only)

DRUG

Caffeine

Caffeine 200mg, oral, by mouth (Cohort 2 only)

DRUG

Qsymia

Qsymia (topiramate 92mg CR, phentermine 15mg PO), oral, by mouth (Cohort 2 only)

DRUG

Topiramate

Topiramate 200mg, oral, by mouth (Cohort 2 only)

BEHAVIORAL

Phentermine

Phentermine 37.5mg, oral, by mouth (Cohort 2 only)

DRUG

Naltrexone

Naltrexone 100mg, oral, by mouth (Cohort 2 only)

DRUG

Mirabegron 50mg

Mirabegron 50mg, oral, by mouth (Cohort 3 only)

DRUG

Mirabegron 200mg

Mirabegron 200mg, oral, by mouth (Cohort 3 only)

DRUG

Placebo Cohort 1

Placebo, oral, by mouth (Cohort 1 only)

DRUG

Placebo Cohort 2

Placebo, oral, by mouth (Cohort 2 only)

DRUG

Placebo for Mirabegron

Placebo for Mirabegron, oral, by mouth (Cohort 3 only)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  lead NIH

Principal Investigators

• Kong Y Chen, Ph.D. · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-02-07

Primary Completion

2022-12-17

Completion

2024-06-11

FDA Drug

Yes

Countries

• United States

Study Locations