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Completed

NCT Number: NCT01791114

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

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.

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Key information

Conditions

Insulin Sensitivity Body Weight Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Texas Medical Branch at Galveston

Galveston, Texas, 77555, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Cold exposure

Other

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).

Cold exposure plus propranolol

Other

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.

Thermoneutral Conditions

Other

Subjects will be exposed to thermoneutral conditions (26 - 28°C)

Cold water consumption

Other

Subjects will be asked to consume cold water (4 °C,10 ml/ kg body weight within 10 minutes)

Tepid water consumption

Other

Subjects will be asked to consume cold water (36 C,10 ml/ kg body weight within 10 minutes)

Exercise

Other

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

Meal consumption

Other

Subjects will be asked to consume a high calorie meal (12 kcal/kg, 50% carbohydrates, 30% fat, and 20% protein) within 15 minutes.

Primary outcomes

  1. Insulin Sensitivity

    Time frame: After 8hrs of cold exposure or thermoneutral conditions

    Insulin sensitivity will be measured using the euglycemic hyperinsulinemic insulin clamp method

Secondary outcomes

  1. 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).

Other outcomes

  1. 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.

  2. 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.

Sponsors and collaborators

Lead sponsor

Rutgers University

Other

Registry information

Important dates

Study start
2012
Primary completion
2018
Study completion
2018
First posted
Feb 13, 2013
Registry last updated
Mar 16, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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