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

March 12, 2021 updated by: Labros Sidossis, Ph.D., Rutgers University
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); on thermoregulation (Aim 3). 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 4). 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Galveston, Texas, United States, 77555
        • University of Texas Medical Branch at Galveston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 hypomotility disorder
  • cancer
  • thyroid or hormone replacement treatment
  • beta-blockers
  • anabolic or corticosteroids 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
  • impaired cognition
  • asthma
  • chronic obstructive pulmonary disease (COPD) or other reactive airway diseases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: Thermoneutral Conditions
Subjects will be exposed to 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.
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% of their maximal oxygen consumption (VO2max) with 15-min breaks between each bout

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin Sensitivity
Time Frame: After 8hrs of cold exposure or thermoneutral conditions
Insulin sensitivity will be measured using the euglycemic hyperinsulinemic insulin clamp method
After 8hrs of cold exposure or thermoneutral conditions

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
During the 8hr trial or on the following day

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
During the 8hr study
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.
During the first 5-6 hrs of the cold exposure study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rutgers University

Investigators

  • Principal Investigator: Labros Sidossis, PhD, University of Texas Medical Branch at Galveston

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Actual)

December 30, 2018

Study Completion (Actual)

December 30, 2018

Study Registration Dates

First Submitted

February 11, 2013

First Submitted That Met QC Criteria

February 12, 2013

First Posted (Estimate)

February 13, 2013

Study Record Updates

Last Update Posted (Actual)

March 16, 2021

Last Update Submitted That Met QC Criteria

March 12, 2021

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11-193

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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