Clinical trial NCT03276442: Biorhythms in Metabolic Tissues
Official title: Biological Rhythms in Metabolic Tissues: Impact of Diet
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sleep Deprivation
Metabolic Disturbance
Biological Clocks
Healthy
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: The Swedish Research Council
First posted: 2017-09-08
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 32
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be studied in a crossover design both after a "healthy diet", and after an "unhealthy diet"
Primary purpose: BASIC_SCIENCE

Brief summary: Metabolism is increasingly recognized as being highly regulated by anticipatory biological rhythms (circadian rhythms or "biorhythms"), which are driven by molecular feedback loops, and which are approximately 24 hours long ("circa diem"). These circadian rhythms exist both centrally, in the brain, but also in the periphery, and are specific to many tissues depending on their main biological function or functions. Whereas these circadian rhythms have been thoroughly characterized in other organisms, their role in humans remain poorly understood, partly because of the difficulty in studying these rhythms in peripheral tissues. The investigators therefore aim to characterize these rhythms in primarily skeletal muscle and adipose tissue in healthy young volunteers (using the so-called constant routine paradigm), and how these rhythms interact with one another at various genetic and molecular levels. At the same time, the investigators aim to study how an unhealthy vs. healthy diet can alter these circadian rhythms, and how they interact with circadian rhythms in other tissue compartments such as those expressed by blood cells.


Eligibility criteria: Inclusion Criteria:

* Age 18-33 yr
* Healthy (self-reported) and not on medication
* BMI 18-28 kg/m2 (and waist circumference \<102 cm), and weight stable (±5% body weight in past 6 months)
* Non-smoker and non-nicotine user
* Regular sleep-wake pattern, with sleep duration of 7-9.25 hrs per night
* Sedentary to moderately active with regular exercise habits the last 2 months
* Regular daily meal pattern with 3 main meals

Exclusion Criteria:

* Major or chronic illness, e.g. diabetes, renal disease or inflammatory bowel disease
* Current or history of endocrine or metabolic disorders
* Psychiatric or neurological disorders (e.g. bipolar disorder, epilepsy)
* Frequent gastrointestinal symptoms
* Chronic medication
* Any sleep disorder (e.g. irregular bedtimes, symptoms of insomnia)
* Any issues with or allergies against the provided food items or utilized anesthesia
* Shift work in the preceding three months or for a long duration
* Time travel over two time zones in the preceding month
* Too much weight gain or weight loss in the preceding 6 months
* Pregnancy

Primary outcomes:
measure: Changes in clock gene & associated omic circadian rhythms
timeFrame: Measured repeatedly (every 6 hours for 24 hours) during a period of extended wakefulness, following each dietary intervention (i.e. over a total period of 6-7 weeks)
Secondary outcomes:
measure: Wakefulness-induced changes and subsequent recovery at omic levels
timeFrame: Following each dietary intervention (i.e. over a total period of 6-7 weeks), measured repeatedly (every 2-6 hours for 24 hours) during a period of extended wakefulness, and after recovery sleep
measure: 24-h rhythms in blood
timeFrame: Measured repeatedly (every 2-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
measure: Diet-induced changes in gut microbiota and relation to circadian rhythms
timeFrame: Measured throughout study participation, i.e. on average over 6-7 weeks
measure: Energy expenditure rhythms
timeFrame: Measured repeatedly (every 2 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
measure: Urine metabolite rhythms
timeFrame: Measured throughout study participation, i.e. on average over 6-7 weeks
measure: Rhythms of blood markers of damage to the central nervous system
timeFrame: Measured repeatedly (every 1-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
measure: 24-h rhythms in saliva
timeFrame: Measured repeatedly (every 2-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
measure: Central circadian rhythms
timeFrame: Measured repeatedly (every 1-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Department of Neuroscience, Uppsala University
Study officials:
affiliation: Uppsala University
name: Jonathan Cedernaes
role: PRINCIPAL_INVESTIGATOR
References: