Clinical trial NCT02261168: Day-Night Rhythm in Human Skeletal Muscle
Official title: Day-night Rhythm in Human Skeletal Muscle Metabolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Insulin Resistance
Keywords: Circadian Rhythm
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2014-10-10
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in healthy lean subjects. Subjects will stay at the research facility for 44 hours with a standardized living protocol during which several measurements of skeletal muscle and whole body energy metabolism will be performed.

Detailed description: Recent evidence from both observational and experimental studies indicates that disobeying our normal day-night rhythm negatively influences our metabolic and cardiovascular health, possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent research indicates that also skeletal muscle mitochondrial function under the influence of a day-night rhythm. The main objective of this study is to investigate the presence of a day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function) of healthy young participants. Therefore, subjects will stay at the research unit for 44 hours, with standardized meals and sleeping time. During this period we will take five muscle biopsies, perform indirect calorimetry measurements and blood draws.

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)

Exclusion Criteria:

* Extreme early bird or extreme night person (score ≤30 or ≥70 on MEQ-SA questionnaire)
* Heavily varying sleep-wake rhythm
* Shiftwork during last 3 months
* Travel across \>1 time zone in the last 3 months
* Engagement in exercise \> 2 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
* Any contra-indication to Magnetic Resonance Imaging (MRI) scanning

Primary outcomes:
measure: Day-night rhythm in skeletal muscle mitochondrial respiration
timeFrame: 40 hours.
Secondary outcomes:
measure: Day-night rhythm in whole-body energy metabolism
timeFrame: 40 hours.
measure: Day-night rhythm in muscle DNA, mRNA and protein levels of markers involved in molecular clock and mitochondrial metabolism.
timeFrame: 40 hours.
measure: Day-night rhythm of in markers of normal day-night rhythm (cortisol, melatonin, core body temperature)
timeFrame: measured during the 2nd study day
measure: Day-night rhythm in blood metabolic compounds (e.g. glucose, insulin, FFA's, cholesterol)
timeFrame: measured during the 2nd study day
measure: Day-night rhythm of molecular clock mRNA and protein levels in blood PBMC's
timeFrame: measured during the 2nd study day
measure: Change in liver volume and liver lipid concentration during the day
timeFrame: First study day 6 PM, second study day 7 AM
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
Study officials:
affiliation: Professor
name: Patrick Schrauwen, PhD
role: PRINCIPAL_INVESTIGATOR
References: