Circadian Rhythmicity in Cold-induced Thermogenesis

NCT ID: NCT04406922

Last Updated: 2021-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-23
• Study Completion Date: 2021-01-01

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.

Conditions

Healthy; Obese; Glucose Intolerance

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Intervention group

Cold exposure in the morning and evening.

Group Type: EXPERIMENTAL

Personalized cooling protocol

Intervention Type: PROCEDURE

As an intervention, a personalized cooling protocol will be used in order to activate BAT and induce non-shivering thermogenesis. During the cooling procedure, subjects will be exposed to mild cold (approx. 14°C) for 150 min. Since the onset temperature of shivering shows a high interindividual variation, we will use a personal cooling protocol to ensure maximum non-shivering EE (and thus an equal maximum activation of BAT). The right temperature will be determined via a subjective method, e.g. to ask the subject if he or she experiences shivering. The time needed to achieve the right temperature is approximately 30-60 minutes. Then, the stable cooling period of 90 min is started. During this time the subject will be asked every 15 minutes whether he is experiencing shivering. If so, temperature will be increased with 2-3°C so that shivering just stops.

Interventions

Personalized cooling protocol

As an intervention, a personalized cooling protocol will be used in order to activate BAT and induce non-shivering thermogenesis. During the cooling procedure, subjects will be exposed to mild cold (approx. 14°C) for 150 min. Since the onset temperature of shivering shows a high interindividual variation, we will use a personal cooling protocol to ensure maximum non-shivering EE (and thus an equal maximum activation of BAT). The right temperature will be determined via a subjective method, e.g. to ask the subject if he or she experiences shivering. The time needed to achieve the right temperature is approximately 30-60 minutes. Then, the stable cooling period of 90 min is started. During this time the subject will be asked every 15 minutes whether he is experiencing shivering. If so, temperature will be increased with 2-3°C so that shivering just stops.

Intervention Type: PROCEDURE

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

mrboon

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mariette R Boon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Leiden University Medical Center

Leiden, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 36319877 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35176767 (View on PubMed)

Other Identifiers

COLD_RHYTHM

Identifier Type: -

Identifier Source: org_study_id