The Effects of Acute Total Sleep Deprivation Versus Normal Sleep on Metabolism

The Role of Acute Total Sleep Deprivation in the Regulation of Metabolism, Neuroendocrine Responses, and Behavioral Measures

The study proposes to investigate whether acute total deprivation affects metabolism as measured through blood and peripheral tissues. Its aim is also to investigate how acute total sleep deprivation affects neurodegenerative markers, as well as hormones, memory performance and aspects of appetite regulation.

Study Overview

• Status: Completed
• Conditions: Sleep; Sleep Deprivation
• Intervention / Treatment: Behavioral: Portion Size Task; Behavioral: Inhibitory task; Procedure: Blood samples; Procedure: Tissue samples; Procedure: Oral glucose tolerance test

Detailed Description

It is predicted that acute total sleep deprivation will affect gene expression and DNA methylation. It is also predicted that sleep deprivation will up-regulate ghrelin, and affect other neuroendocrine markers and hormones in a negative manner. It is further predicted that sleep deprivation will decrease participants' memory performance.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, 75324
    • Department of Neuroscience, Uppsala University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 28 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• Age 18-28y
• Healthy (self-reported) and not on medication
• Non-smoking
• Normal sleep-wake rhythm (i.e. 7-8 h per night, self-reported via diaries)

Exclusion Criteria:

• Major illness
• Taking any serious medications
• Any sleep conditions (e.g. irregular bedtimes, sleep complaints)
• Any dietary issues with the food items provided
• Current or history of endocrine, neurological or psychiatric disorders
• Shift work in the preceding three months or for a long duration
• Time travel over a significant number of time zones in the preceding two months
• Too much weight gain or weight loss in the preceding three months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Total sleep deprivation; Participants will be required to stay up for the entire night before 'Blood Samples' and 'Tissue samples' will be taken and the 'Portion Size Task' and 'Inhibitory task' will be performed. This will then be followed by the 'Oral glucose tolerance test' with additional 'Blood Samples' to be taken as described for that test.	Behavioral: Portion Size Task; Participants are given a computer program that gives them the opportunity to choose the portions of a variety of food items that they would ideally like to consume; Behavioral: Inhibitory task; Participants perform a binary decision on each presented stimuli. Of the two possible outcomes, participants are instructed to make a motor response (go) for one type, and are to withhold a response (no-go) for the other type. Reaction time and accuracy are measured for each event; Procedure: Blood samples; Hormone levels, neuromolecular levels and gene expression profiles will be analyzed from repeated blood samples obtained before and after the nighttime intervention; Procedure: Tissue samples; Expression profiles will be analyzed from samples obtained from tissues involved in metabolism; Procedure: Oral glucose tolerance test; 75 g of glucose will be dissolved in 300 ml of water and given to participants, followed by blood sampling at 0, 15, 30, 60, 90, 120 and 150 minutes following the ingestion of the glucose solution.
Experimental: Sleep; Participants will have an 8-h sleep opportunity before 'Blood Samples' and 'Tissue samples' will be taken and 'Portion Size Task' and 'Inhibitory task' will be performed. This will be followed by the 'Oral glucose tolerance test' with additional 'Blood Samples' to be taken as described for that test.	Behavioral: Portion Size Task; Participants are given a computer program that gives them the opportunity to choose the portions of a variety of food items that they would ideally like to consume; Behavioral: Inhibitory task; Participants perform a binary decision on each presented stimuli. Of the two possible outcomes, participants are instructed to make a motor response (go) for one type, and are to withhold a response (no-go) for the other type. Reaction time and accuracy are measured for each event; Procedure: Blood samples; Hormone levels, neuromolecular levels and gene expression profiles will be analyzed from repeated blood samples obtained before and after the nighttime intervention; Procedure: Tissue samples; Expression profiles will be analyzed from samples obtained from tissues involved in metabolism; Procedure: Oral glucose tolerance test; 75 g of glucose will be dissolved in 300 ml of water and given to participants, followed by blood sampling at 0, 15, 30, 60, 90, 120 and 150 minutes following the ingestion of the glucose solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene expression and DNA methylation	This study has been designed to measure the changes in gene expression and DNA methylation in circulating blood, i.e. mainly of white blood cells with active transcription and DNA regulation, and how this relates to possible changes in peripheral tissues involved in metabolism.	Change from baseline (ie. around 1930 in the evening - before sleep intervention) to 12 hours later (around 0730 in the morning after the nighttime intervention), and to 15 hours later (around 1030 in the morning after the nighttime intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating hormone and neuromolecular levels	Participants will have their circulating hormone levels and neuromolecular levels taken and analyzed, including ghrelin, to determine if sleep deprivation alters hormone and neuromolecular levels related primarily to obesity, cognition or weight gain	Change in circulating hormone levels from baseline (ie. around 1930 in the evening - before sleep intervention) to 12 hours later (around 0730 in the morning after the nighttime intervention)
Appetitive evaluation	Participants will be evaluated on their appetitive ratings in the morning following either nighttime intervention (acute total sleep deprivation or normal 8-hour sleep).	Change in appetitive ratings after the sleep intervetion (from around 0700 in the morning after the nighttime intervention), repeated each hour
Portion Size Task	Participants will be evaluated on their tendency to choose larger or smaller portions of a variety of meal items on a computer screen. This will be conducted both following partial sleep deprivation and normal sleep, and changes before and after glucose ingestion will be compared between these conditions	Change in selected portion size in the morning, at around 0830 hours in the morning following each nighttime intervention, and 2h30min later, i.e. 30 min after consuming an Oral glucose tolerance test, i.e. around 1100 hours
Inhibitory task	Participants perform a binary decision on each presented stimuli. Of the two possible outcomes, participants are instructed to make a motor response (go) for one type, and are to withhold a response (no-go) for the other type. Reaction time and accuracy are measured for each event.	Change in cognitive inhibitory performance at around 0810 hours in the morning following the respective nighttime intervention.

Collaborators and Investigators

• Sponsor: Uppsala University
• Investigators: Principal Investigator: Christian Benedict, PhD, Department of Neuroscience, Uppsala University

Publications and helpful links

General Publications

• Mateus Brandao LE, Espes D, Westholm JO, Martikainen T, Westerlund N, Lampola L, Popa A, Vogel H, Schurmann A, Dickson SL, Benedict C, Cedernaes J. Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial. J Sleep Res. 2022 Apr;31(2):e13472. doi: 10.1111/jsr.13472. Epub 2021 Sep 2.
• Cedernaes J, Osler ME, Voisin S, Broman JE, Vogel H, Dickson SL, Zierath JR, Schioth HB, Benedict C. Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men. J Clin Endocrinol Metab. 2015 Sep;100(9):E1255-61. doi: 10.1210/JC.2015-2284. Epub 2015 Jul 13.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: February 21, 2013
• First Submitted That Met QC Criteria: February 25, 2013
• First Posted (Estimate): February 27, 2013

Study Record Updates

• Last Update Posted (Estimate): December 9, 2013
• Last Update Submitted That Met QC Criteria: December 6, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Sleep Deprivation
• Other Study ID Numbers: SleepMetaJCCB2013