Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue

NCT ID: NCT01783470

Last Updated: 2019-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2014-10-31

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.

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.

Conditions

Obesity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

beta3-adrenergic receptor agonist

Intervention Type: DRUG

single dose. The subjects were randomized to receive placebo on one study day and active beta3-adrenergic receptor agonist on the other study day.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

mirabegron, which is Myrbetriq (TM) by Astellas Pharma

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

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

NIH

Sponsor Role: collaborator

Aaron Cypess

OTHER

Sponsor Role: lead

Responsible Party

Aaron Cypess

Investigator, NIDDK, NIH

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Aaron M Cypess, MD PhD

Role: PRINCIPAL_INVESTIGATOR

NIDDK, NIH

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

References

Cypess AM, Weiner LS, Roberts-Toler C, Franquet Elia E, Kessler SH, Kahn PA, English J, Chatman K, Trauger SA, Doria A, Kolodny GM. Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab. 2015 Jan 6;21(1):33-8. doi: 10.1016/j.cmet.2014.12.009.

Reference Type: RESULT

PMID: 25565203 (View on PubMed)

Other Identifiers

2P30DK036836-26

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2012P000309

Identifier Type: -

Identifier Source: org_study_id