Day-Night Rhythm in Human Skeletal Muscle

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Day-night Rhythm in Human Skeletal Muscle Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02261168
• Other study ID #: METC143027
• Secondary ID: NL49363.068.14
• Status: Completed
• Phase: N/A
• First received: September 24, 2014
• Last updated: September 4, 2015
• Start date: November 2014
• Est. completion date: July 2015

Study information

• Verified date: September 2015
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Insulin Resistance

Intervention

Other:
• Standardized living protocol
Subjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements.

Locations

Country	Name	City	State
Netherlands	Maastricht University	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Day-night rhythm in skeletal muscle mitochondrial respiration	O2-flux (pmol/mg/s) measured with high resolution respirometry upon administration of different substrates	40 hours.	No
Secondary	Day-night rhythm in whole-body energy metabolism	Energy expenditure (kJ/min), glucose oxidation (g/min) and fat oxidation (g/min) measured by indirect calorimetry	40 hours.	No
Secondary	Day-night rhythm in muscle DNA, mRNA and protein levels of markers involved in molecular clock and mitochondrial metabolism.	Quantify mRNA and protein levels by qPCR or micro-array and Western blots	40 hours.	No
Secondary	Day-night rhythm of in markers of normal day-night rhythm (cortisol, melatonin, core body temperature)	Blood cortisol and melatonin levels and core body temperature measured by an ingested telemetric pill.	measured during the 2nd study day	No
Secondary	Day-night rhythm in blood metabolic compounds (e.g. glucose, insulin, FFA's, cholesterol)		measured during the 2nd study day	No
Secondary	Day-night rhythm of molecular clock mRNA and protein levels in blood PBMC's	Measured by qPCR and Western Blots	measured during the 2nd study day	No
Secondary	Change in liver volume and liver lipid concentration during the day	Measured by Magnetic Resonance Imaging and -Spectroscopy (MRI/MRS). Lipid signals in the MRS spectra will be quantified while suppressing the strong water signal in the region of interest (right liver lobe)	First study day 6 PM, second study day 7 AM	No