Shivering and Glucose Homeostasis
Primary Purpose
Healthy Overweight/Obese
Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Cold exposure
Sponsored by

About this trial
This is an interventional treatment trial for Healthy Overweight/Obese focused on measuring Type 2 diabetes mellitus, Shivering thermogenesis, skeletal muscle
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent
- Caucasian
- Healthy (as determined by dependent physician based on medical questionnaire)
- Man, or postmenopausal (defined as at least 1year post cessation of menses) woman
- Aged 40 - 75 years at the start of the study
- BMI 27 and 35 kg/m2
- Stable dietary habits (no weight loss or gain >3kg in the past 3 months)
Exclusion Criteria:
- - Not meeting all inclusion criteria
- Medication use known to hamper subject's safety during study procedures
- Co-morbidities to which the intervention or program that may pose as a complicating factor
- Subjects diagnosed with cardiovascular diseases or cancer
- Fasting plasma glucose ≥ 7.0 mmol/l
- Haemoglobin < 7.8 mmol/l for women, or < 8.4 mmol/l for men
- Previously diagnosed with type 2 diabetes
- Abuse alcohol/drug abuse
- Subjects who do not want to be informed about unexpected medical findings during the screening/study or do not wish that their physician is informed.
- Engagement in structured exercise > 2h per week
- Participation in another biomedical study within 1 month before the first study
- Smoking
- Cold-acclimated, such as takes daily extended cold baths, works in a refrigerated environment, or regular cold-water swimming within 1 month of starting the study
Sites / Locations
- Maastricht University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cold acclimation arm
Arm Description
An oral glucose tolerance test will be performed on day 1 of the study. The next day (day 2), subjects will be exposed to shivering thermogenesis for at least 1 hour. The day after, an oral glucose tolerance test will be performed (day 3). The following 9 days, subjects will be exposed daily to shivering thermogenesis for at least 1 hour (day 4-12). On the last day (day 13), an oral glucose tolerance test will be performed.
Outcomes
Primary Outcome Measures
area under the curve (AUC) of the glucose tolerance test
area under the curve (AUC) of the glucose tolerance test before cold exposure, 1 day after cold exposure and after 9 consecutive days of cold exposure.
Secondary Outcome Measures
skeletal muscle GLUT4 translocation
Comparison between skeletal muscle GLUT4 translocation, as assessed by wide-field microscopy both before and after cold acclimation
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04516018
Brief Title
Shivering and Glucose Homeostasis
Official Title
The Effect of Prolonged Shivering Thermogenesis on Glucose Homeostasis in Overweight/Obese Humans
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
December 13, 2021 (Actual)
Study Completion Date
December 13, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to investigate the effect of prolonged shivering thermogenesis on glucose homeostasis in overweight/obese humans.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Overweight/Obese
Keywords
Type 2 diabetes mellitus, Shivering thermogenesis, skeletal muscle
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
a single arm, longitudinal study (10-day intermittent shivering exposure) in a pre-post design
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cold acclimation arm
Arm Type
Experimental
Arm Description
An oral glucose tolerance test will be performed on day 1 of the study. The next day (day 2), subjects will be exposed to shivering thermogenesis for at least 1 hour. The day after, an oral glucose tolerance test will be performed (day 3). The following 9 days, subjects will be exposed daily to shivering thermogenesis for at least 1 hour (day 4-12). On the last day (day 13), an oral glucose tolerance test will be performed.
Intervention Type
Other
Intervention Name(s)
Cold exposure
Intervention Description
Subjects will be exposed to shivering thermogenesis for at least 1 hour for 10 days
Primary Outcome Measure Information:
Title
area under the curve (AUC) of the glucose tolerance test
Description
area under the curve (AUC) of the glucose tolerance test before cold exposure, 1 day after cold exposure and after 9 consecutive days of cold exposure.
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Secondary Outcome Measure Information:
Title
skeletal muscle GLUT4 translocation
Description
Comparison between skeletal muscle GLUT4 translocation, as assessed by wide-field microscopy both before and after cold acclimation
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Other Pre-specified Outcome Measures:
Title
Insulin sensitivity
Description
Comparison between insulin sensitivity as estimated from the insulin and glucose concentrations during the OGTT both before and after cold acclimation.
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Heart rate
Description
Comparison between heart rate during cold exposure both before and after cold acclimation
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Blood pressure
Description
Comparison between blood pressure during cold exposure both before and after cold acclimation
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Energy expenditure
Description
Comparison between energy expenditure as assessed by indirect calorimetry both before and after cold acclimation
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Substrate oxidation
Description
Comparison between substrate oxidation as assessed by indirect calorimetry both before and after cold acclimation
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Plasma substrates
Description
Comparison between plasma substrates change during cold acclimation (including insulin, FFA, glucose) both before and after cold acclimation
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Plasma hormones
Description
Comparison between plasma hormones change during cold acclimation (including insulin, FFA, glucose) both before and after cold acclimation
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Skeletal muscle intramyocellular substrate content
Description
Comparison between skeletal muscle intramyocellular substrate content both before and after cold acclimation
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Protein expression in skeletal muscle
Description
Comparison between protein expression in skeletal muscle both before and after cold acclimation of specific pathways as determined by western blot
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Gene expression in skeletal muscle
Description
Comparison between gene expression in skeletal muscle both before and after cold acclimation of specific pathways as determined by RT-qPCR
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Body temperatures
Description
Change in both skin and core temperature upon cold acclimation as assessed by means of temperatures sensors and a core temperature pill
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
Title
Shivering activity
Description
Muscle shivering activity as determined by EMG. Comparison between shivering activity before and after cold acclimation
Time Frame
1 day following cold exposure and following 9 consecutive days of cold exposure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent
Caucasian
Healthy (as determined by dependent physician based on medical questionnaire)
Man, or postmenopausal (defined as at least 1year post cessation of menses) woman
Aged 40 - 75 years at the start of the study
BMI 27 and 35 kg/m2
Stable dietary habits (no weight loss or gain >3kg in the past 3 months)
Exclusion Criteria:
- Not meeting all inclusion criteria
Medication use known to hamper subject's safety during study procedures
Co-morbidities to which the intervention or program that may pose as a complicating factor
Subjects diagnosed with cardiovascular diseases or cancer
Fasting plasma glucose ≥ 7.0 mmol/l
Haemoglobin < 7.8 mmol/l for women, or < 8.4 mmol/l for men
Previously diagnosed with type 2 diabetes
Abuse alcohol/drug abuse
Subjects who do not want to be informed about unexpected medical findings during the screening/study or do not wish that their physician is informed.
Engagement in structured exercise > 2h per week
Participation in another biomedical study within 1 month before the first study
Smoking
Cold-acclimated, such as takes daily extended cold baths, works in a refrigerated environment, or regular cold-water swimming within 1 month of starting the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wouter van Marken Lichtenbelt, Prof.
Organizational Affiliation
Maastricht University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maastricht University
City
Maastricht
State/Province
Limburg
ZIP/Postal Code
6229ER
Country
Netherlands
12. IPD Sharing Statement
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Shivering and Glucose Homeostasis
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