Circadian Rhythmicity in Cold-induced Thermogenesis

Not Applicable

Completed

• Conditions: Healthy; Obese; Glucose Intolerance
• Interventions: Procedure: Personalized cooling protocol

• Registration Number: NCT04406922
• Lead Sponsor: Leiden University Medical Center

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.

Study Timeline

• Study Start: 2019-04-23
• Study First Submitted: 2020-01-21
• Study First Submitted QC: 2020-05-24
• Study First Posted: 2020-05-29
• Primary Completion: 2021-01-01
• Study Completion: 2021-01-01
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-14
• Last Update Posted: 2021-04-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention group	Personalized cooling protocol	Cold exposure in the morning and evening.

Primary Outcome Measures

Name	Time	Method
Change in cold-induced non-shivering thermogenesis between morning and evening	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.	Thermogenesis is estimated by the change in energy expenditure after cold exposure, measured by indirect calorimetry. This will be measured in the morning and in the evening.

Secondary Outcome Measures

Name	Time	Method
Change in insulin (pmol/l)	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.	Serum insulin (pmol/l) before and during cold exposure in the morning versus in the evening.
Change in markers for sympathetic output	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.	Norepinephrine, epinephrine (μM/ml)
Change in lipid metabolism (cholesterol) (mmol/L)	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.	Cholesterol (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) in serum (mmol/L). Before and during cold exposure in the morning and in the evening.
Skin temperature	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.	Wireless iButtons and infrared camera
Change in glucose metabolism (mmol/L)	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.	Serum glucose (mmol/L) before and during cold exposure in the morning versus the evening.
Change in lipid metabolism (triglycerides) (mmol/L)	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.	Triglycerides, glycerol and free fatty acids in serum (mmol/L). Before and during cold exposure in the morning and in the evening.

Trial Locations

Locations (1)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands