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The Effect of Brown Adipose Tissue Activation on Insulin Sensitivity in Humans

This study is currently recruiting participants.
Verified February 2013 by The University of Texas, Galveston
Sponsor:
Information provided by (Responsible Party):
The University of Texas, Galveston
ClinicalTrials.gov Identifier:
NCT01791114
First received: February 11, 2013
Last updated: February 12, 2013
Last verified: February 2013
  Purpose

Recent findings document the presence of active brown adipose tissue (BAT) in humans. Cold exposure via adrenergic stimulation activates BAT, which combusts significant amounts of blood glucose and free fatty acid (FFA) to produce heat. Animal studies suggest that BAT activation improves insulin sensitivity. However, the effect of cold-induced BAT activation on insulin sensitivity and glucose kinetics in humans remains unknown. The investigators' central hypothesis is that cold-induced BAT activation increases whole body insulin sensitivity in humans via augmented plasma glucose and FFA clearance. The specific aims of this study are to define the effects of prolonged (8h) cold exposure BAT activation on: insulin sensitivity (Aim 1); lipolysis and plasma glucose and FFA kinetics (Aim 2). Moreover, the investigators plan to investigate for alternative ways, which can activate BAT including cold water ingestion, a single meal ingestion, and a single bout of moderate intensity exercise (Aim 3). For the cold exposure study, subjects will complete 3 trials: a) 8hrs of cold exposure at their individually determined shivering threshold; b) 8hrs of cold exposure at their individually determined shivering threshold plus propranolol; c) 8hrs in thermoneutral conditions (26 - 28°C). For the rest of the arms of subjects will complete two trials: cold or tepid water ingestion, a single meal ingestion or no food ingestion, and a single bout of moderate intensity exercise or no exercise.To study the above aims, the investigators will use positron emission tomography - computed tomography, hyperinsulinemic euglycemic clamp, infusion of stable isotopes, and tissue biopsies. The findings will illuminate the role of BAT on plasma substrate regulation and insulin sensitivity and may aid in the development of lifestyle recommendations and pharmacotherapy for the prevention and treatment of diabetes and insulin resistance.


Condition Intervention
Insulin Sensitivity
Obesity
Other: Cold exposure
Other: Cold exposure plus propranolol
Other: Thermoneutral Conditions
Other: Cold water consumption
Other: Tepid water consumption
Other: Exercise
Other: Meal consumption

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science

Resource links provided by NLM:


Further study details as provided by The University of Texas, Galveston:

Primary Outcome Measures:
  • Insulin Sensitivity [ Time Frame: After 8hrs of cold exposure or thermoneutral conditions ] [ Designated as safety issue: No ]
    Insulin sensitivity will be measured using the euglycemic hyperinsulinemic insulin clamp method


Secondary Outcome Measures:
  • Metabolic profile [ Time Frame: During the 8hr trial or on the following day ] [ Designated as safety issue: No ]
    Evaluation of metabolic profile will include measurement of various metabolites (glucose, triglycerides, very low-density (VLDL)-triglycerides, non-esterified fatty acids, lipoproteins, apo-B) and hormones (leptin, adiponectin, insulin, ghrelin).


Other Outcome Measures:
  • Substrate kinetics [ Time Frame: During the 8hr study ] [ Designated as safety issue: No ]
    We will use a stable isotopes to assess substrate kinetics. Specifically, a primed, constant 4hr infusion of 6,6-D2-glucose to assess glucose kinetics; b) a constant 4hr infusion of potassium uniformly labelled with carbon 13 [U-13C16] palmitate to assess FFA kinetics (27, 28); and c) a primed, constant, 4hr infusion of [1,1,2,3,3-2H5]glycerol dissolved in 0.9% NaCl solution, to assess whole body lipolysis , and) a bolus of labeled with carbon13 sodium bicarbonate(NaHCO3) dissolved in 09% sodium chloride (NaCl) solution to assess substrate oxidation.


Estimated Enrollment: 30
Study Start Date: January 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cold water consumption
Subjects will participate in two trials as part of this protocol: a) cold water (4 °C) consumption and b) tepid (36  °C) water consumption
Other: Cold water consumption
Subjects will be asked to consume cold water (4 °C,10 ml/ kg body weight within 10 minutes)
Other: Tepid water consumption
Subjects will be asked to consume cold water (36 C,10 ml/ kg body weight within 10 minutes)
Experimental: Meal consumption
Subjects will participate in two trials as part of this protocol: a) High calorie meal consumption and two weeks later b) no meal consumption.
Other: Thermoneutral Conditions
Subjects will be exposed to thermoneutral conditions (26 - 28°C)
Other: Meal consumption
Subjects will be asked to consume a high calorie meal (12 kcal/kg, 50% carbohydrates, 30% fat, and 20% protein) within 15 minutes.
Experimental: Cold exposure
Participants will complete three studies: a) cold exposure study (above their individually determined shivering threshold ~ 16°C); b) Cold exposure plus 40-80 mg propranolol; c) thermoneutral conditions (26 - 28°C).
Other: Cold exposure
For the cold exposure trial, the subjects will follow an individualized cold exposure protocol maximize the elicited non-shivering thermogenesis. Subjects will be wearing liquid conditioned garments (Polar Products Inc, Stow, OH). The temperature will initially be set at 18°C, then decreased at 1 degree celsius intervals thought the air- conditioned temperature control bath until subjects report shivering. Electromyography (EMG; Delsys, Bagnoli 8, Boston, MA) will be performed continuously to verify shivering muscle activity. Upon shivering, the temperature will be increased by 1degree Celsius intervals until shivering resides. Subjects' core temperature will be measured at 10-second intervals with the use of a telemetric pill (Core Temp Inc., Palmetto, FL).
Other: Cold exposure plus propranolol
For the cold exposure plus propanol trial, temperature will be titrated similarly to the cold exposure study. The non-selective beta-adrenergic antagonist propranolol (40-80 mg) will be given orally before the beginning of the study and again after 4 hours. The dose will be titrated to achieve a 20% decrease in heart rate from the subject's own 24-hour average resting heart rate of the cold exposure trials. Heart rate and blood pressure will be monitored continuously throughout the study. Propranolol doses up to 80 mg have been shown to significantly reduce fluoro-deoxy-glucose (FDG) uptake in brown fat in clinical patients.
Other: Thermoneutral Conditions
Subjects will be exposed to thermoneutral conditions (26 - 28°C)
Experimental: Exercise
Subjects between 18 and 35 years old will be asked to participate in two trials: a) Exercise, i.e. four times for 10 min- at 85% VO2max (maximal oxygen consumption). with 15-min breaks between each bout b) and two weeks later rest.
Other: Thermoneutral Conditions
Subjects will be exposed to thermoneutral conditions (26 - 28°C)
Other: Exercise
Subject will be asked to complete four bouts of exercise for 10 min- at 85% VO2max with 15-min breaks between each bout

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • men or women
  • 18-75 years old
  • BMI 20-40 kg/m2

Exclusion Criteria:

  • taking diabetes medications
  • liver/renal/endocrine/heart disease
  • obstructive disease of the gastrointestinal tract
  • impaired gag reflex or swallowing disorder
  • history of GI surgery or fenilization of esophagus
  • GI hypomolitity disorder
  • cancer
  • thyroid or hormone replacement treatment
  • beta-blockers
  • anabolic or cortico-steroids the last 6 mo
  • pregnant/lactating women
  • individuals that are likely to need PET/CT in the near future for medical reasons
  • bleeding disorders/ anemia
  • positive hepatitis or HIV screening
  • weight less than 36 kg
  • pacemaker or other implanted electromedical device
  • alcohol and drug abuse
  • tobacco use
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01791114

Contacts
Contact: Labros Sidossis, PhD 409.266.9690 lasidoss@utmb.edu
Contact: Maria Chondronikola, MS, RD 6462442920 machondr@utmb.edu

Locations
United States, Texas
University of Texas Medical Branch at Galveston Recruiting
Galveston, Texas, United States, 77555
Contact: Labros Sidossis, PhD    409-266-9690    lasidoss@utmb.edu   
Principal Investigator: Labros S Sidossis, PhD         
Sponsors and Collaborators
The University of Texas, Galveston
Investigators
Principal Investigator: Labros Sidossis, PhD University of Texas Medical Branch at Galveston
  More Information

No publications provided

Responsible Party: The University of Texas, Galveston
ClinicalTrials.gov Identifier: NCT01791114     History of Changes
Other Study ID Numbers: 11-193
Study First Received: February 11, 2013
Last Updated: February 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas, Galveston:
Insulin sensitivity
Diabetes Prevention
Obesity
Brown adipose tissue

Additional relevant MeSH terms:
Insulin Resistance
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Propranolol
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vasodilator Agents

ClinicalTrials.gov processed this record on April 17, 2014