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Circadian Rhythmicity in Cold-induced Thermogenesis (COLDR)

Primary Purpose

Healthy, Obese, Glucose Intolerance

Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Personalized cooling protocol
Sponsored by
Leiden University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Healthy focused on measuring lean, young, healthy, overweight, obese

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • Leiden University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention group

Arm Description

Cold exposure in the morning and evening.

Outcomes

Primary Outcome Measures

Change in cold-induced non-shivering thermogenesis between morning and evening
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

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

Full Information

First Posted
January 21, 2020
Last Updated
April 14, 2021
Sponsor
Leiden University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04406922
Brief Title
Circadian Rhythmicity in Cold-induced Thermogenesis
Acronym
COLDR
Official Title
The Impact of Circadian Rhythmicity in Cold-induced Thermogenesis in Lean and Obese Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
April 23, 2019 (Actual)
Primary Completion Date
January 1, 2021 (Actual)
Study Completion Date
January 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Obese, Glucose Intolerance
Keywords
lean, young, healthy, overweight, obese

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
The study design encompasses a single-arm randomized intervention study using cold exposure.
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention group
Arm Type
Experimental
Arm Description
Cold exposure in the morning and evening.
Intervention Type
Procedure
Intervention Name(s)
Personalized cooling protocol
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in cold-induced non-shivering thermogenesis between morning and evening
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Change in glucose metabolism (mmol/L)
Description
Serum glucose (mmol/L) before and during cold exposure in the morning versus the evening.
Time Frame
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.
Title
Change in insulin (pmol/l)
Description
Serum insulin (pmol/l) before and during cold exposure in the morning versus in the evening.
Time Frame
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.
Title
Change in lipid metabolism (cholesterol) (mmol/L)
Description
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.
Time Frame
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.
Title
Change in lipid metabolism (triglycerides) (mmol/L)
Description
Triglycerides, glycerol and free fatty acids in serum (mmol/L). Before and during cold exposure in the morning and in the evening.
Time Frame
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.
Title
Change in markers for sympathetic output
Description
Norepinephrine, epinephrine (μM/ml)
Time Frame
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.
Title
Skin temperature
Description
Wireless iButtons and infrared camera
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mariette R Boon, MD, PhD
Organizational Affiliation
Leiden University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333ZA
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36319877
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.
Results Reference
derived
PubMed Identifier
35176767
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.
Results Reference
derived

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Circadian Rhythmicity in Cold-induced Thermogenesis

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