Clinical trial NCT01783470: Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue
Official title: Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Keywords: adipose tissue, brown
obesity
Adrenergic beta-3 Receptor Agonists
thermogenesis
metabolism
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2013-02-05
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: BAT Activity as Measured by 18F-FDG PET/CT
timeFrame: 60 min after FDG administration
Secondary outcomes:
Other outcomes:
measure: Whole-body Energy Expenditure
timeFrame: 30 minutes before drug administration followed by 30 minutes after FDG administration
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: NIDDK, NIH
name: Aaron M Cypess, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.