Insulin SensitivityNCT01791114
The Effect of Brown Adipose Tissue Activation on Insulin Sensitivity in Humans
A study testing Cold exposure, Cold exposure plus propranolol and Thermoneutral Conditions in people with Insulin Sensitivity and Obesity, run by Rutgers University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Sensitivity, Obesity
- What is being tested?
- Cold exposure, Cold exposure plus propranolol and Thermoneutral Conditions
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to 30 Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- men or women
- 18-75 years old
- BMI 20-40 kg/m2
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Medical Branch at Galveston
Galveston, Texas, 77555
About this study
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.
- Conditions
- Insulin Sensitivity, Obesity
- Being tested
- Cold exposure, Cold exposure plus propranolol, Thermoneutral Conditions, Cold water consumption, Tepid water consumption
- Keywords
- Insulin sensitivity, Diabetes Prevention, Obesity, Brown adipose tissue
- Medical subject headings
- Insulin Resistance, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cold exposureOther
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 propranololOther
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 ConditionsOther
Subjects will be exposed to thermoneutral conditions (26 - 28°C)
Cold water consumptionOther
Subjects will be asked to consume cold water (4 °C,10 ml/ kg body weight within 10 minutes)
Tepid water consumptionOther
Subjects will be asked to consume cold water (36 C,10 ml/ kg body weight within 10 minutes)
ExerciseOther
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 consumptionOther
Subjects will be asked to consume a high calorie meal (12 kcal/kg, 50% carbohydrates, 30% fat, and 20% protein) within 15 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Cold water consumption | Experimental | Subjects will participate in two trials as part of this protocol: a) cold water (4 °C) consumption and b) tepid (36 °C) water consumption Receives: Other: Cold water consumption; Other: Tepid water consumption |
| Meal consumption | Experimental | Subjects will participate in two trials as part of this protocol: a) High calorie meal consumption and two weeks later b) no meal consumption. Receives: Other: Thermoneutral Conditions; Other: Meal consumption |
| Cold exposure | Experimental | 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). Receives: Other: Cold exposure; Other: Cold exposure plus propranolol; Other: Thermoneutral Conditions |
| Exercise | Experimental | 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. Receives: Other: Thermoneutral Conditions; Other: Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Sensitivity
Insulin sensitivity will be measured using the euglycemic hyperinsulinemic insulin clamp method
Measured: After 8hrs of cold exposure or thermoneutral conditions
Secondary outcomes (1)
Metabolic profile
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).
Measured: During the 8hr trial or on the following day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2013 (estimated)
- Study startJan 2012
- Primary completion30 Dec 2018
- Study completion30 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Insulin SensitivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rutgers University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Labros Sidossis, Ph.D., Rutgers University
- Investigators
- Labros Sidossis, PhD, Principal investigator, The University of Texas Medical Branch, Galveston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01791114
- Sponsor's protocol ID
- 11-193
- Status last verified
- Jan 2019
- First submitted
- 11 Feb 2013
- Last updated
- 16 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 27148068Chondronikola 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.
PubMed 25056438
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Brown Adipose Tissue Activation on Insulin Sensitivity in Humans
- ClinicalTrials.gov ID
- NCT01791114
- Acronym / sponsor ID
- 11-193
- Conditions
- Insulin Sensitivity, Obesity
- Keywords
- Insulin sensitivity, Diabetes Prevention, Obesity, Brown adipose tissue
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Rutgers UniversityUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- 30 Dec 2018 (actual)
- Study completion
- 30 Dec 2018 (actual)
- First posted
- 13 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cold water consumption | Experimental | Other: Cold water consumption, Other: Tepid water consumptionSubjects will participate in two trials as part of this protocol: a) cold water (4 °C) consumption and b) tepid (36 °C) water consumption |
| Meal consumption | Experimental | Other: Thermoneutral Conditions, Other: Meal consumptionSubjects will participate in two trials as part of this protocol: a) High calorie meal consumption and two weeks later b) no meal consumption. |
| Cold exposure | Experimental | Other: Cold exposure, Other: Cold exposure plus propranolol, Other: Thermoneutral ConditionsParticipants 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). |
| Exercise | Experimental | Other: Thermoneutral Conditions, Other: ExerciseSubjects 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- men or women
- 18-75 years old
- BMI 20-40 kg/m2
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cold exposureFor 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 |
| Cold exposure plus propranololFor 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 | Cold exposure |
| Thermoneutral ConditionsSubjects will be exposed to thermoneutral conditions (26 - 28°C) | Other | Cold exposure, Exercise, Meal consumption |
| Cold water consumptionSubjects will be asked to consume cold water (4 °C,10 ml/ kg body weight within 10 minutes) | Other | Cold water consumption |
| Tepid water consumptionSubjects will be asked to consume cold water (36 C,10 ml/ kg body weight within 10 minutes) | Other | Cold water consumption |
| ExerciseSubject 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 | Other | Exercise |
| Meal consumptionSubjects will be asked to consume a high calorie meal (12 kcal/kg, 50% carbohydrates, 30% fat, and 20% protein) within 15 minutes. | Other | Meal consumption |
Primary outcome
Insulin Sensitivity
Time frame: After 8hrs of cold exposure or thermoneutral conditions
Insulin sensitivity will be measured using the euglycemic hyperinsulinemic insulin clamp method
1 secondary outcome
Metabolic profile
Time frame: During the 8hr trial or on the following day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2021.
- Derived from this study: PubMed 27148068Chondronikola 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.
- Derived from this study: PubMed 25056438Chondronikola 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Labros Sidossis, PhD principal investigator
The University of Texas Medical Branch, Galveston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cold exposure, Cold exposure plus propranolol and Thermoneutral Conditions in people with Insulin Sensitivity and Obesity, run by Rutgers University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin Sensitivity (time frame: After 8hrs of cold exposure or thermoneutral conditions). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01791114, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2021.