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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Sleep Deprivation, Sleep

Intervention / Treatment
-----------------
* Behavioral: Inhibitory task
* Procedure: Blood samples
* Procedure: Tissue samples
* Procedure: Oral glucose tolerance test
* Behavioral: Portion Size Task


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 28 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Total sleep deprivation<br>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: Inhibitory task<br>* 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<br>Procedure: Blood samples<br>* Hormone levels, neuromolecular levels and gene expression profiles will be analyzed from repeated blood samples obtained before and after the nighttime intervention<br>Procedure: Tissue samples<br>* Expression profiles will be analyzed from samples obtained from tissues involved in metabolism<br>Procedure: Oral glucose tolerance test<br>* 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.<br>Behavioral: Portion Size Task<br>* 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<br>|
| Experimental: Sleep<br>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: Inhibitory task<br>* 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<br>Procedure: Blood samples<br>* Hormone levels, neuromolecular levels and gene expression profiles will be analyzed from repeated blood samples obtained before and after the nighttime intervention<br>Procedure: Tissue samples<br>* Expression profiles will be analyzed from samples obtained from tissues involved in metabolism<br>Procedure: Oral glucose tolerance test<br>* 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.<br>Behavioral: Portion Size Task<br>* 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<br>|

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. |