Impact of Circadian Misalignment on Insulin Sensitivity

Circadian Misalignment and Insulin Sensitivity

Sponsors

Lead sponsor: Maastricht University Medical Center

Source Maastricht University Medical Center
Brief Summary

This study will evaluate the effect of circadian misalignment on insulin sensitivity in healthy lean subjects in a randomized cross-over design. Subjects will be admitted to the research facility for two study periods of 3 and 3.5 days. In one of the study periods, the behavioral cycle will be shifted by 12 hours. Insulin sensitivity will be measured with a hyperinsulinemic euglycemic clamp.

Detailed Description

Recent evidence shows that misalignment of the circadian rhythm (e.g. by rotating shift work) impairs glucose metabolism markedly, possibly by decreasing insulin sensitivity in peripheral tissues and liver. Nowadays our society is indispensably connected to a lifestyle that allows wakefulness at every time of the 24 hours cycle. Social jetlag is a phenomenon that affects a large part of the general population, thus circadian misalignment extends far beyond those who are on a shift work schedule. Therefore, decreased insulin sensitivity in individuals affected by circadian misalignment may help to explain the increased prevalence of T2DM in night shift workers that has been found in epidemiological studies.

The study is an interventional randomized crossover trial in which each subject serves as it owns control. For the study, the investigators ask the subjects to participate in two study periods, one of 3 days length (control condition) and the other of 3.5 days length (misalignment condition). During the 3.5 day misalignment condition, subjects will shift their day-night rhythm by 12 hours, which will lead to maximal circadian misalignment. Insulin sensitivity will be measured by a hyperinsulinemic euglycemic clamp. Secondary parameters will include ex-vivo skeletal muscle mitochondrial function and whole-body energy metabolism.

Overall Status Completed
Start Date January 2016
Completion Date February 2017
Primary Completion Date February 2017
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Insulin Sensitivity 2 days after circadian misalignment and matched time in control arm.
Secondary Outcome
Measure Time Frame
Oxidative glucose disposal 2 days after circadian misalignment and matched time in control arm.
Non-oxidative glucose disposal 2 days after circadian misalignment and matched time in control arm.
Skeletal muscle mitochondrial function 1 and 2 days after circadian misalignment and matched times in control arm
Whole body energy metabolism while awake 1 and 2 days after circadian misalignment and matched times in control arm
Sleeping metabolic rate 1.5 days after circadian misalignment and matched time in control arm
Skeletal muscle mtDNA 1 and 2 days after circadian misalignment and matched times in control arm
Skeletal muscle mRNA 1 and 2 days after circadian misalignment and matched times in control arm
Skeletal muscle proteins 1 and 2 days after circadian misalignment and matched times in control arm
Metabolic compounds in the blood (e.g. glucose, insulin, FFA's, Triglycerides, cholesterol) 1 and 2 days after circadian misalignment and matched times in control arm
Core-body-temperature 1 day after circadian misalignment and matched time in control arm
Peripheral skin temperature 1 day after circadian misalignment and matched time in control arm
Central skin temperature 1 day after circadian misalignment and matched time in control arm
Heart rate 1 day after circadian misalignment and matched time in control arm
Enrollment 14
Condition
Intervention

Intervention type: Behavioral

Intervention name: Circadian Misalignment

Arm group label: Circadian Misalignment

Eligibility

Criteria:

Inclusion Criteria:

- Caucasian

- Healthy (as determined by dependent physician based on medical questionnaire)

- Male

- Age: 18-35 years

- Normal BMI (18-25 kg/m2)

- Regular sleeping time (normally 7 - 9h daily)

- Habitual bedtime at 11 PM ± 2 hours

Exclusion Criteria:

- Extreme early bird or extreme night person

- Heavily varying sleep-wake rhythm

- Shiftwork during last 3 months

- Travel across >1 time zone in the last 3 months

- Engagement in exercise > 3 hours total per week

- Using > 400mg caffeine daily

- Smoking

- Unstable body weight (weight gain or loss > 3kg in the last 3 months)

- Significant food allergies/intolerance (seriously hampering study meals)

- Participation in another biomedical study within 1 month before the first study visit

- Claustrophobia

- Medication use hampering the study (as determined by responsible physician)

- Recent blood donation.

- Any contra-indication to the telemetric pill:

- Any acute condition, exacerbation of chronic condition, or medical history that would in the investigator's opinion interfere with the study

Gender: Male

Minimum age: 18 Years

Maximum age: 35 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Patrick Schrauwen, PhD Principal Investigator Maastricht University Medical Center
Location
facility Maastricht University
Location Countries

Netherlands

Verification Date

June 2017

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Control

Arm group type: No Intervention

Description: 3 days with normal circadian alignment.

Arm group label: Circadian Misalignment

Arm group type: Experimental

Description: 3.5 days in which the subjects will undergo a maximal circadian misalignment of 12 hours by means of a midday nap during the second day, and a subsequent start of a new normal wake period, shifted 12 hours.

Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov