Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Aaron Cypess, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01783470
First received: January 29, 2013
Last updated: August 20, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Obesity
Drug: beta3-adrenergic receptor agonist
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effects of b3-Adrenergic Receptor Agonists on Brown Adipose Tissue

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • BAT activity as measured by 18F-FDG PET/CT [ Time Frame: 60 min after FDG administration ] [ Designated as safety issue: No ]
    difference in BAT activity measured in placebo and active drug arms


Secondary Outcome Measures:
  • plasma norepinephrine [ Time Frame: 5 minutes before FDG administration ] [ Designated as safety issue: No ]
    difference in the plasma concentration of norepinephrine measured in the placebo and active drug arms


Estimated Enrollment: 15
Study Start Date: February 2013
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
lactose
Drug: Placebo
Other Name: Lactose
Experimental: beta3-adrenergic receptor agonist
single dose
Drug: beta3-adrenergic receptor agonist
single dose

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01783470

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Aaron Cypess
Investigators
Principal Investigator: Aaron M Cypess, MD, PhD Beth Israel Deaconess Medical Center & Joslin Diabetes Center
  More Information

No publications provided

Responsible Party: Aaron Cypess, Assistant Professor, Harvard Medical & Staff Physician, Joslin Diabetes Center, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01783470     History of Changes
Other Study ID Numbers: 2012-P-000309, 2P30DK036836-26
Study First Received: January 29, 2013
Last Updated: August 20, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
adipose tissue, brown
obesity
Adrenergic beta-3 Receptor Agonists
thermogenesis
metabolism

Additional relevant MeSH terms:
Obesity
Body Weight
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014