Biorhythms in Metabolic Tissues

Healthy Clinical Trial

Official title:

Biological Rhythms in Metabolic Tissues: Impact of Diet

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03276442
• Other study ID #: CircHFJC2017
• Status: Recruiting
• Phase: N/A
• First received: August 28, 2017
• Last updated: October 10, 2017
• Start date: August 31, 2017
• Est. completion date: December 31, 2019

Study information

• Verified date: October 2017
• Source: Uppsala University
• Contact: Jonathan Cedernaes, M.D., Ph.D.
• Phone: 0184714136
• Email: jonathan.cedernaes[@]neuro.uu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 31, 2019
• Est. primary completion date: November 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 32 Years

Eligibility

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

Related Conditions & MeSH terms

• Biological Clocks
• Healthy
• Metabolic Disturbance
• Sleep Deprivation

Intervention

Other:
• Low-fat dietary intervention
Low-fat diet (5-7 days) preceding extended wakefulness under standardized conditions
• High-fat dietary intervention
High-fat diet (5-7 days) preceding extended wakefulness under standardized conditions

Locations

Country	Name	City	State
Sweden	Department of Neuroscience, Uppsala University	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	The Swedish Research Council

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in clock gene & associated omic circadian rhythms	Changes in clock gene & associated clock-regulated & clock-independent metabolic and omic circadian rhythms (e.g. in epigenome, transcriptome, metabolites) in peripheral tissues (primarily skeletal muscle and adipose tissue), and interplay between these rhythms across the 24-h period and under the different dietary conditions	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	Wakefulness-induced changes and subsequent recovery at omic levels	Changes at omic levels (e.g. DNA methylation, transcriptome, proteome, metabolome) in peripheral tissues (primarily skeletal muscle and adipose tissue), urine and feces samples due to extended wakefulness following subsequent recovery, following each dietary intervention	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
Secondary	24-h rhythms in blood	Changes in rhythms in blood-borne cells, proteins and other molecular factors such as DNA, hormones, and proteins, due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions	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)
Secondary	Diet-induced changes in gut microbiota and relation to circadian rhythms	Changes in gut microbiota (metagenomic, compositional) due to dietary intervention, and relation to circadian rhythms measured across 24 hrs in peripheral tissues following the two dietary conditions	Measured throughout study participation, i.e. on average over 6-7 weeks
Secondary	Energy expenditure rhythms	Changes in energy expenditure rhythms due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions	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)
Secondary	Urine metabolite rhythms	Changes in levels of urine metabolites due to dietary intervention, and relation to circadian rhythms across 24 hrs in peripheral tissues following the two dietary conditions	Measured throughout study participation, i.e. on average over 6-7 weeks
Secondary	Rhythms of blood markers of damage to the central nervous system	Assessment of rhythms in of blood markers of damage to the central nervous system (e.g. Olink Proseek multiplex panel, neuron-specific enolase, S-100b) across a 24-h period and following subsequent recovery sleep, following the two dietary conditions	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)
Secondary	24-h rhythms in saliva	Changes in rhythms in saliva-borne cells, proteins and other molecular factors such as DNA, hormones, and proteins, due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions	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)
Secondary	Central circadian rhythms	Changes in centrally driven circadian rhythms (e.g. temperature and melatonin), due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions	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)