Circadian Rhythmicity in Cold-induced Thermogenesis (COLDR)

April 14, 2021 updated by: mrboon, Leiden University Medical Center

The Impact of Circadian Rhythmicity in Cold-induced Thermogenesis in Lean and Obese Subjects

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Leiden, Netherlands, 2333ZA
        • Leiden University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 35 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Intervention group
Cold exposure in the morning and evening.
Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in cold-induced non-shivering thermogenesis between morning and 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.
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.
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 Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in glucose metabolism (mmol/L)
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.
Serum glucose (mmol/L) before and during cold exposure in the morning versus the evening.
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.
Change in insulin (pmol/l)
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.
Serum insulin (pmol/l) before and during cold exposure in the morning versus in the evening.
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.
Change in lipid metabolism (cholesterol) (mmol/L)
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.
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 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.
Change in lipid metabolism (triglycerides) (mmol/L)
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.
Triglycerides, glycerol and free fatty acids in serum (mmol/L). Before and during cold exposure in the morning and in the evening.
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.
Change in markers for sympathetic output
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.
Norepinephrine, epinephrine (μM/ml)
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.
Skin temperature
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.
Wireless iButtons and infrared camera
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Leiden University Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mariette R Boon, MD, PhD, Leiden University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 23, 2019

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2021

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 21, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 24, 2020

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 29, 2020

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 19, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 14, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • COLD_RHYTHM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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