Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01783470
Recruitment Status : Active, not recruiting
First Posted : February 5, 2013
Results First Posted : May 11, 2017
Last Update Posted : May 11, 2017
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Aaron Cypess, Beth Israel Deaconess Medical Center

Brief Summary:
This study will test the hypothesis that human brown adipose tissue (BAT) can be activated using a β3-adrenergic receptor (AR) agonist. The efficacy of β3-AR agonist will be compared with cold exposure, which we have already shown can activate human BAT, as well as a placebo control.

Condition or disease Intervention/treatment Phase
Obesity Drug: beta3-adrenergic receptor agonist Phase 2

Detailed Description:

This study will include an outpatient screening visit and three separate, independent overnight study visits in the General Clinical Research Center (GCRC) at Beth Israel Deaconess Medical Center (BIDMC). Screening procedures will consist of a medical history, physical examination, blood draw, and ECG. If, from the screening tests, it is determined that the eligibility criteria have been meet, healthy volunteers will participate in three separate inpatient visits at BIDMC. Study procedures will occur in the GCRC and the Nuclear Medicine suite at BIDMC.

Volunteers will first complete Day A, in which we will measure BAT volume and activity during cold exposure. Cold exposure will consist of wearing a cooling vest at 55 - 61°F, a temperature shown to be cool enough to activate brown adipose tissue but warm enough not to lead to shivering. Resting metabolic rate (RMR) will be measured by indirect calorimetry before and during cool exposure.

If there is detectable brown fat activity on Day A, volunteers will participate in Days B and C. Days B and C will be conducted in random order to reduce any bias from the sequence of treatment and scans, as well as any potential placebo effects. Day B will consist of pharmacological stimulation with β3-AR agonist. On Day C, volunteers will be given a placebo control and will not undergo cooling.

A blood draw of 26 cc will always be done prior to FDG injection and FDG PET/CT will always be performed 60 minutes after FDG injection. On Day A, FDG will be injected after 60 minutes of cool exposure and the volunteer will remain in the cooling vest for another 60 minutes after FDG injection.

To compare energy expenditure and BAT mass and activity among volunteers, we will normalize the data to fat and muscle mass. Whole-body and regional fat and muscle mass will be measured via a Dual Energy X-ray Absorptiometry (DXA) scan at the end of Day A.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue
Study Start Date : February 2013
Actual Primary Completion Date : December 2015
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
Experimental: beta3-adrenergic receptor agonist
single dose. Each subject was randomized to receive placebo at one visit and then the beta3-adrenergic receptor agonist on another study day.
Drug: beta3-adrenergic receptor agonist
single dose. The subjects were randomized to receive placebo on one study day and active beta3-adrenergic receptor agonist on the other study day.
Other Name: mirabegron, which is Myrbetriq (TM) by Astellas Pharma

Primary Outcome Measures :
  1. BAT Activity as Measured by 18F-FDG PET/CT [ Time Frame: 60 min after FDG administration ]
    difference in BAT metabolic activity measured in placebo and active drug arms. The BAT metabolic activity represents the amount of FDG tracer retained within the tissue. Retained FDG is a biomarker for tissue oxygen consumption and hence energy expenditure by the tissue.

Other Outcome Measures:
  1. Whole-body Energy Expenditure [ Time Frame: 30 minutes before drug administration followed by 30 minutes after FDG administration ]
    This is the energy expenditure as calculated using indirect calorimetry.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Healthy Male
  • 18-65 years old
  • BMI between 18-40
  • Not participated in clinical trial and received either an investigational or marketed drug within two months prior to the study
  • Not donated blood in previous two months

Exclusion Criteria:

  • Women
  • History of local or systemic infection disease with fever or requiring antibiotic within 4 weeks of drug administration
  • Corrected QT interval above normal
  • Laboratory test results that is more than 1.5 fold outside normal range and/or is judged to be clinically significant
  • Current addition to alcohol or substances of abuse
  • Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation
  • Use of system course of corticosteroids or other medication known to cause insulin resistance in previous 6 weeks
  • Hyperthyroidism,hypothyroidism, hypertension (even if controlled with medications), heart disease (including CAD and CHF), cardiac arrhythmias, diabetes, unstable vasomotor system, or use of monoamine oxidase (MAO) inhibitors
  • Diagnosis of bladder outlet obstruction or use of any medication to treat overactive bladder (e.g. Tolterodine, Solifenacin, Propiverine, Oxybutynin, and Fesoterodine)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01783470

United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Aaron Cypess
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Aaron M Cypess, MD PhD NIDDK, NIH

Publications of Results:
Responsible Party: Aaron Cypess, Investigator, NIDDK, NIH, Beth Israel Deaconess Medical Center Identifier: NCT01783470     History of Changes
Other Study ID Numbers: 2012P000309
2P30DK036836-26 ( U.S. NIH Grant/Contract )
First Posted: February 5, 2013    Key Record Dates
Results First Posted: May 11, 2017
Last Update Posted: May 11, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Aaron Cypess, Beth Israel Deaconess Medical Center:
adipose tissue, brown
Adrenergic beta-3 Receptor Agonists

Additional relevant MeSH terms:
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-3 Receptor Agonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists