Biorhythms in Metabolic Tissues

NCT03276442 | Unknown

• 1 other identifier: CircHFJC2017
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Sleep Deprivation; Metabolic Disturbance; Biological Clocks; Healthy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Wakefulness-induced changes and subsequent recovery at omic levels

  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

• 24-h rhythms in blood

  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)

• Diet-induced changes in gut microbiota and relation to circadian rhythms

  Measured throughout study participation, i.e. on average over 6-7 weeks

• Energy expenditure rhythms

  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)

• Urine metabolite rhythms

  Measured throughout study participation, i.e. on average over 6-7 weeks

Study Arms (2)

Healthy diet

EXPERIMENTAL

'Low-fat dietary intervention' to be administered to participants

Other: Low-fat dietary intervention

Unhealthy diet

EXPERIMENTAL

'High-fat dietary intervention' to be administered to participants

Other: High-fat dietary intervention

Interventions

Low-fat dietary intervention OTHER

Low-fat diet (5-7 days) preceding extended wakefulness under standardized conditions

Healthy diet

High-fat dietary intervention OTHER

High-fat diet (5-7 days) preceding extended wakefulness under standardized conditions

Unhealthy diet

Eligibility Criteria

• Age: 18 Years - 32 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Uppsala University: lead
• The Swedish Research Council: collaborator

Study Sites (1)

Department of Neuroscience, Uppsala University

Uppsala, 75324, Sweden

RECRUITING

Related Publications (1)

• Brandao LEM, Popa A, Cedernaes E, Cedernaes C, Lampola L, Cedernaes J. Exposure to a more unhealthy diet impacts sleep microstructure during normal sleep and recovery sleep: A randomized trial. Obesity (Silver Spring). 2023 Jul;31(7):1755-1766. doi: 10.1002/oby.23787. Epub 2023 May 28.

  PMID: 37245331 DERIVED

MeSH Terms

Conditions

Sleep Deprivation

Condition Hierarchy (Ancestors)

Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Study Officials

• Jonathan Cedernaes

  Uppsala University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonathan Cedernaes, M.D., Ph.D.

CONTACT

0184714136; jonathan.cedernaes@neuro.uu.se

Christian Benedict, Ph.D.

CONTACT

0184714136; christian.benedict@neuro.uu.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: In the crossover subgroup condition, participants will not be briefed about what diet they will receive before the actual onset of the dietary intervention
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be studied in a crossover design both after a "healthy diet", and after an "unhealthy diet"

Study Record Dates

• First Submitted: August 28, 2017
• First Posted: September 8, 2017
• Study Start: August 31, 2017
• Primary Completion: November 30, 2019
• Study Completion: December 31, 2019
• Last Updated: October 12, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)