Clinical trial NCT03096535: Cold Induced Activation of Brown Adipose Tissue in Humans
Official title: Cold Induced Activation of Brown Fat in Humans Assessed With PET/MR Scans and Skin-temperature Measure - A Cross-over Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Adipose Tissue, Brown
Brown Adipose Tissue
Brown Fat
Uncoupling Protein 1
Adipokines
Proteomics
Infrared Thermography
BAT
Obesity
Type 2 Diabetes
Proteins
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2017-03-30
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study investigates cold-induced brown fat activation assessed using PET/MR scans. Subjects will participate in an acute cooling intervention day and a thermoneutral intervention day with PET/MR scans on both days. A secondary purpose is to make a validation of an infrared thermography camera by comparison of skin temperatures and SUV of the supraclavicular brown adipose tissue.

Detailed description: The field of human brown adipose tissue (BAT) research is focused on activation of BAT as a means of manipulating energy expenditure and potentially anti-obesity and anti-diabetic properties of the tissue. This is well established in rodent studies and explained as due to the specific brown fat uncoupling protein 1 (UCP1). Despite increasing evidence that indicates a metabolic regulatory role of BAT in humans, BAT activation/recruitment is not fully understood and even less is known about the endocrine capacities of human BAT.

Cold induced brown fat activity will be assessed with PET/MR scans and validate an infra-red thermography camera, as well as perform a proteomic screening using blood samples under these two intervention days.

15 healthy lean male subjects will serve as their own control in a cross-over randomized control study, including a pre-examination day, a thermoneutral-day and a cooling test-day with cold exposure followed by a PET/MR scan to determine BAT activity. An extra cooling day is applied for the external validation of the infrared thermography camera. Blood samples and abdominal fat-biopsies will be taken at thermoneutral condition and under cold stimulation of brown fat.

Eligibility criteria: Inclusion Criteria:

* Age 18-30 years.
* Men
* Caucasian white
* Body Mass Index 19-25 kg/m2.
* Moderate physical activity level (not more than 8-10 hours of training pr. Week)
* Ability to give informed consent.
* Ability to follow verbal and written instructions in Danish.
* Body fat percent under 21% measured at the pre-examination day.

Exclusion Criteria:

* Chronic diseases: Hormonal: Metabolic Diseases mb. Graves, hypothyroidism, myxedema and goiter. Diabetes Melitus, Coronary heart disease (history of myocardial infarction, unstable angina pectoris, or congestive heart failure), cancer treated within last 3 years.
* Tobacco, marijuana or intravenous drug use within 1 year of screening.
* Dieting, recent weight loss (\>3 kg within 3 month) or a history of an eating disorder.
* Dietary supplements.
* History of depression, psychosis, or other psychiatric illness requiring hospitalization.
* Alcohol consumption \>14 units/week.
* History of alcohol abuse within the past 3 years.
* Known liver disease or elevated liver biomarkers more than 2 times upper normal levels in the preliminary investigation.
* Known kidney disease or elevated kidney biomarkers, eCRF \<60 ml/min, in the preliminary investigation.
* Use of daily medications, except for seasonal use of antihistamines.
* Diagnosed sleep disturbances.
* Pacemaker or other electronics implanted in the body.
* Magnetic impressionable metal implants or foreign objects in the body inconsistent with completion of MR.
* Claustrophobia
* Communication problems, including understanding the experimental protocol
* History of contrast allergy.
* Winter swimmers.

Primary outcomes:
measure: Difference in brown adipose tissue (BAT) activity after cooling versus no cooling.
timeFrame: Difference in SUV mean after 2 hours of cooling versus 2 hours of no cooling.
Secondary outcomes:
measure: Difference in BAT activity after cooling versus no cooling.
timeFrame: Difference in peak temperature after 2 hours of cooling versus 2 hours of no cooling.
measure: Difference in resting energy expenditure after cooling versus no cooling
timeFrame: Difference in resting energy expenditure after 2 hours of cooling versus 2 hours of no cooling.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Center for Inflammation and Metabolism/ Center for Physical Activity Research
Study officials:
affiliation: Center for Inflammation and Metabolism/Center for physical activity research
name: Susanna Søberg, MSc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Soberg S, Lofgren J, Philipsen FE, Jensen M, Hansen AE, Ahrens E, Nystrup KB, Nielsen RD, Solling C, Wedell-Neergaard AS, Berntsen M, Loft A, Kjaer A, Gerhart-Hines Z, Johannesen HH, Pedersen BK, Karstoft K, Scheele C. Altered brown fat thermoregulation and enhanced cold-induced thermogenesis in young, healthy, winter-swimming men. Cell Rep Med. 2021 Oct 11;2(10):100408. doi: 10.1016/j.xcrm.2021.100408. eCollection 2021 Oct 19.