Shivering and Glucose Homeostasis

• ClinicalTrials.gov Identifier: NCT04516018
• Recruitment Status: Completed
• First Posted: August 17, 2020
• Last Update Posted: January 14, 2022
• Sponsor: Maastricht University
• Information provided by (Responsible Party): Maastricht University

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.

Condition or disease	Intervention/treatment	Phase
Healthy Overweight/Obese	Other: Cold exposure	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: a single arm, longitudinal study (10-day intermittent shivering exposure) in a pre-post design
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Prolonged Shivering Thermogenesis on Glucose Homeostasis in Overweight/Obese Humans
• Actual Study Start Date: September 1, 2020
• Actual Primary Completion Date: December 13, 2021
• Actual Study Completion Date: December 13, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Cold acclimation arm; 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.

Other: Cold exposure; Subjects will be exposed to shivering thermogenesis for at least 1 hour for 10 days

Outcome Measures

Primary Outcome Measures :

1. area under the curve (AUC) of the glucose tolerance test [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   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 :

1. skeletal muscle GLUT4 translocation [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between skeletal muscle GLUT4 translocation, as assessed by wide-field microscopy both before and after cold acclimation

Other Outcome Measures:

1. Insulin sensitivity [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between insulin sensitivity as estimated from the insulin and glucose concentrations during the OGTT both before and after cold acclimation.
2. Heart rate [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between heart rate during cold exposure both before and after cold acclimation
3. Blood pressure [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between blood pressure during cold exposure both before and after cold acclimation
4. Energy expenditure [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between energy expenditure as assessed by indirect calorimetry both before and after cold acclimation
5. Substrate oxidation [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between substrate oxidation as assessed by indirect calorimetry both before and after cold acclimation
6. Plasma substrates [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between plasma substrates change during cold acclimation (including insulin, FFA, glucose) both before and after cold acclimation
7. Plasma hormones [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between plasma hormones change during cold acclimation (including insulin, FFA, glucose) both before and after cold acclimation
8. Skeletal muscle intramyocellular substrate content [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between skeletal muscle intramyocellular substrate content both before and after cold acclimation
9. Protein expression in skeletal muscle [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
   Comparison between protein expression in skeletal muscle both before and after cold acclimation of specific pathways as determined by western blot
10. Gene expression in skeletal muscle [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
    Comparison between gene expression in skeletal muscle both before and after cold acclimation of specific pathways as determined by RT-qPCR
11. Body temperatures [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
    Change in both skin and core temperature upon cold acclimation as assessed by means of temperatures sensors and a core temperature pill
12. Shivering activity [ Time Frame: 1 day following cold exposure and following 9 consecutive days of cold exposure ]
    Muscle shivering activity as determined by EMG. Comparison between shivering activity before and after cold acclimation

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Netherlands

Maastricht University

Maastricht, Limburg, Netherlands, 6229ER

Sponsors and Collaborators

Maastricht University

Investigators

• Principal Investigator: Wouter van Marken Lichtenbelt, Prof.; Maastricht University

More Information

• Responsible Party: Maastricht University
• ClinicalTrials.gov Identifier: NCT04516018
• Other Study ID Numbers: NL73487.068.20
• First Posted: August 17, 2020
• Last Update Posted: January 14, 2022
• Last Verified: January 2022

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

Keywords provided by Maastricht University:

Type 2 diabetes mellitus; Shivering thermogenesis; skeletal muscle

Additional relevant MeSH terms:

Overweight; Body Weight