HealthyCOLDRNCT04406922
Circadian Rhythmicity in Cold-induced Thermogenesis
A study testing Personalized cooling protocol in people with Healthy and Obese, run by Leiden University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Obese, Glucose Intolerance
- What is being tested?
- Personalized cooling protocol
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 23 Apr 2019to 1 Jan 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Being tested
- Personalized cooling protocol
- Keywords
- lean, young, healthy, overweight, obese
- Medical subject headings
- Obesity, Glucose Intolerance, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Personalized cooling protocolProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Cold exposure in the morning and evening. Receives: Procedure: Personalized cooling protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (6)
Change in glucose metabolism (mmol/L)
Serum glucose (mmol/L) before and during cold exposure in the morning versus the evening.
Measured: 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)
Serum insulin (pmol/l) before and during cold exposure in the morning versus in the evening.
Measured: 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)
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.
Measured: 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)
Triglycerides, glycerol and free fatty acids in serum (mmol/L). Before and during cold exposure in the morning and in the evening.
Measured: 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
Norepinephrine, epinephrine (μM/ml)
Measured: 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
Wireless iButtons and infrared camera
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2020
- Study start23 Apr 2019
- Primary completion1 Jan 2021
- Study completion1 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study design encompasses a single-arm randomized intervention study using cold exposure.
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, mrboon, Leiden University Medical Center
- Investigators
- Mariette R Boon, MD, PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04406922
- Sponsor's protocol ID
- COLD_RHYTHM
- Acronym
- COLDR
- Status last verified
- Apr 2021
- First submitted
- 21 Jan 2020
- Last updated
- 19 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36319877Straat 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.
PubMed 35176767
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Circadian Rhythmicity in Cold-induced Thermogenesis in Lean and Obese Subjects
- ClinicalTrials.gov ID
- NCT04406922
- Acronym / sponsor ID
- COLDR / COLD_RHYTHM
- Conditions
- Healthy, Obese, Glucose Intolerance
- Keywords
- lean, young, healthy, overweight, obese
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- 23 Apr 2019 (actual)
- Primary completion
- 1 Jan 2021 (actual)
- Study completion
- 1 Jan 2021 (actual)
- First posted
- 29 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study design encompasses a single-arm randomized intervention study using cold exposure.
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Procedure: Personalized cooling protocolCold exposure in the morning and evening. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Personalized cooling protocolAs 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. | Procedure or surgery | Intervention group |
Primary outcome
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.
6 secondary outcomes
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.
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.
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.
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Derived from this study: PubMed 36319877Sardjoe 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.
- Derived from this study: PubMed 35176767Straat 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mariette R Boon, MD, PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Personalized cooling protocol in people with Healthy and Obese, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04406922, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2021.