Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue

Aaron Cypess

Status and phase

Completed

Phase 2

Conditions

Obesity

Treatments

Drug: beta3-adrenergic receptor agonist

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01783470

2P30DK036836-26 (U.S. NIH Grant/Contract)

2012P000309

Details and patient eligibility

About

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.

Full 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.

Enrollment

15 patients

Sex

Male

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

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)