Clinical trial NCT04406922: Circadian Rhythmicity in Cold-induced Thermogenesis
Official title: The Impact of Circadian Rhythmicity in Cold-induced Thermogenesis in Lean and Obese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Obese
Glucose Intolerance
Keywords: lean
young
healthy
overweight
obese
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2020-05-29
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study design encompasses a single-arm randomized intervention study using cold exposure.
Primary purpose: BASIC_SCIENCE

Brief summary: This study aims to investigate whether maximum cold-induced non-shivering thermogenesis (e.g. thermogenesis as a consequence of BAT activity) differs between morning and evening.

Detailed description: Brown adipose tissue (BAT) recently emerged as a novel player in energy expenditure (EE) in humans as it combusts fatty acids and glucose towards heat. Human BAT can be activated by sympathetic stimulation resulting from cold exposure or treatment with sympathomimetic drugs. Short-term acclimation to mild cold was shown to reduce fat mass in obese subjects and decrease peripheral insulin resistance of patients with T2DM. Recently, in preclinical studies the investigators showed that BAT has a circadian rhythm. It is currently unknown whether this is also the case in humans. The investigators postulate that BAT activity should display a circadian rhythm that adapts to changes in circadian behavior, and may determine glucose/lipid levels throughout the day.

Eligibility criteria: Inclusion Criteria:

* Dutch white Caucasian males or females
* Age: 18-35 years
* Lean group: BMI ≥ 18 and ≤ 25 kg/m2
* Obese glucose tolerant group: BMI ≥ 30 and ≤ 42 kg/m2 and fasted plasma glucose levels \< 5.5 and/or 2 h after OGTT ≤ 7.8 mM
* Obese impaired glucose tolerant group: BMI ≥ 30 and ≤ 42 kg/m2 and fasted plasma glucose levels ≥ 5.5 and/or 2 h after OGTT between 7.8 and 11.1 mM

Exclusion Criteria:

* Diabetes mellitus (determined on basis of fasting or OGTT defined by ADA criteria (30)
* Any other active endocrine disease (thyroid disease, any signs of Cushing's syndrome, adrenal disease and lipid-associated disorders such as familial hypercholesterolemia)
* Any chronic renal or hepatic disease
* Use of medication known to influence glucose and/or lipid metabolism or brown fat activity (e.g. beta blockers, antidepressants)
* Smoking
* Abuse of alcohol or other substances
* Pregnancy
* Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study
* Current participation in another research projects that may influence the current research project
* Clinically relevant abnormalities in clinical chemistry at screening (to be judged by the study physician)

Primary outcomes:
measure: Change in cold-induced non-shivering thermogenesis between morning and evening
timeFrame: Change in cold-induced non-shivering thermogenesis between morning (total duration of measurement 120 minutes) and evening (total duration of measurement 120 minutes). The time frame comprising both the morning and evening measurement will be 72 hours.
Secondary outcomes:
measure: Change in glucose metabolism (mmol/L)
timeFrame: Change between morning and evening: measured at several timepoints during 3.5 hours. The time frame comprising both the morning and evening measurement will be 72 hours.
measure: Change in insulin (pmol/l)
timeFrame: Change between morning and evening: measured at several timepoints during 3.5 hours. The time frame comprising both the morning and evening measurement will be 72 hours.
measure: Change in lipid metabolism (cholesterol) (mmol/L)
timeFrame: Change between morning and evening: measured at severaltime points during 3.5 hours. The time frame comprising both the morning and evening measurement will be 72 hours.
measure: Change in lipid metabolism (triglycerides) (mmol/L)
timeFrame: Change between morning and evening: measured at severaltime points during 3.5 hours. The time frame comprising both the morning and evening measurement will be 72 hours.
measure: Change in markers for sympathetic output
timeFrame: Change between morning and evening: measured before and after cold exposure. The time frame comprising both the morning and evening measurement will be 72 hours.
measure: Skin temperature
timeFrame: Change between morning and evening: measured every 60 seconds during cold exposure on both study days. The time frame comprising both the morning and evening measurement will be 72 hours.
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: Mariette R Boon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sardjoe Mishre ASD, Straat ME, Martinez-Tellez B, Mendez Gutierrez A, Kooijman S, Boon MR, Dzyubachyk O, Webb A, Rensen PCN, Kan HE. The Infrared Thermography Toolbox: An Open-access Semi-automated Segmentation Tool for Extracting Skin Temperatures in the Thoracic Region including Supraclavicular Brown Adipose Tissue. J Med Syst. 2022 Nov 2;46(12):89. doi: 10.1007/s10916-022-01871-7.
citation: Straat ME, Martinez-Tellez B, Sardjoe Mishre A, Verkleij MMA, Kemmeren M, Pelsma ICM, Alcantara JMA, Mendez-Gutierrez A, Kooijman S, Boon MR, Rensen PCN. Cold-Induced Thermogenesis Shows a Diurnal Variation That Unfolds Differently in Males and Females. J Clin Endocrinol Metab. 2022 May 17;107(6):1626-1635. doi: 10.1210/clinem/dgac094.