The Effect of Brown Adipose Tissue Activation on Insulin Sensitivity in Humans
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|ClinicalTrials.gov Identifier: NCT01791114|
Recruitment Status : Recruiting
First Posted : February 13, 2013
Last Update Posted : December 22, 2016
|Condition or disease||Intervention/treatment||Phase|
|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||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Study Start Date :||January 2012|
|Estimated Primary Completion Date :||January 2017|
|Estimated Study Completion Date :||January 2017|
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 0.5mg/kg up to 40mg propranolol at the beginning of the metabolic study and again after 4-6 hrs; 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 as previously described. The non-selective beta-adrenergic antagonist propranolol (0.5mg/kg and up to 40) will be given orally before the beginning of the study and again after 4-6 hours. In case participant's heart rate after propranolol administration decreases below 50 beats per min or systolic blood pressure below 90 mmHg second dose of propranolol will not be administered. Heart rate and blood pressure will be monitored continuously throughout the study. Propranolol doses up to 80 mg have been shown to significantly reduce fludeoxyglucose (FDG) uptake in brown fat in clinical patients.Other: Thermoneutral Conditions
Subjects will be exposed to thermoneutral conditions (26 - 28°C)
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% of their maximal oxygen consumption (VO2max) with 15-min breaks between each bout
- Insulin Sensitivity [ Time Frame: After 8hrs of cold exposure or thermoneutral conditions ]Insulin sensitivity will be measured using the euglycemic hyperinsulinemic insulin clamp method
- Metabolic profile [ Time Frame: During the 8hr trial or on the following day ]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).
- Substrate kinetics [ Time Frame: During the 8hr study ]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.
- Thermoregulation [ Time Frame: During the first 5-6 hrs of the cold exposure study ]We will use a telemetric pill and wireless thermistors to monitor the body core and skin temperatures of the participants. Moreover, thermal sensation will be assessed using a visual analog scale of the American Society of Heating, Refrigerating, and Air-Conditioning Engineers. Heart rate and blood pressure will be also measured to assess the cardiovascular response to cold exposure.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01791114
|Contact: Labros Sidossis, PhDemail@example.com|
|Contact: Maria Chondronikola, MS, RDfirstname.lastname@example.org|
|United States, Texas|
|University of Texas Medical Branch at Galveston||Recruiting|
|Galveston, Texas, United States, 77555|
|Contact: Labros Sidossis, PhD 409-266-9690 email@example.com|
|Principal Investigator: Labros S Sidossis, PhD|
|Principal Investigator:||Labros Sidossis, PhD||University of Texas Medical Branch at Galveston|