Clinical trial NCT01791114: The Effect of Brown Adipose Tissue Activation on Insulin Sensitivity in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Sensitivity
Obesity
Keywords: Insulin sensitivity
Diabetes Prevention
Obesity
Brown adipose tissue
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2013-02-13
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility 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 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

Primary outcomes:
measure: Insulin Sensitivity
timeFrame: After 8hrs of cold exposure or thermoneutral conditions
Secondary outcomes:
measure: Metabolic profile
timeFrame: During the 8hr trial or on the following day
Other outcomes:
measure: Substrate kinetics
timeFrame: During the 8hr study
measure: Thermoregulation
timeFrame: During the first 5-6 hrs of the cold exposure study
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston
state: Texas
Study officials:
affiliation: University of Texas Medical Branch at Galveston
name: Labros Sidossis, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chondronikola M, Volpi E, Borsheim E, Chao T, Porter C, Annamalai P, Yfanti C, Labbe SM, Hurren NM, Malagaris I, Cesani F, Sidossis LS. Brown Adipose Tissue Is Linked to a Distinct Thermoregulatory Response to Mild Cold in People. Front Physiol. 2016 Apr 19;7:129. doi: 10.3389/fphys.2016.00129. eCollection 2016.
citation: Chondronikola M, Volpi E, Borsheim E, Porter C, Annamalai P, Enerback S, Lidell ME, Saraf MK, Labbe SM, Hurren NM, Yfanti C, Chao T, Andersen CR, Cesani F, Hawkins H, Sidossis LS. Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans. Diabetes. 2014 Dec;63(12):4089-99. doi: 10.2337/db14-0746. Epub 2014 Jul 23.