The purpose of this study is to 1) determine how hypothalamic-pituitary-adrenal axis (HPA axis) activation occurs with sleep restriction and 2) evaluate how hypothalamic-pituitary-gonadal axis (HPG axis) deactivation occurs with sleep restriction. The investigator will also examine the cognitive function associated with sleep restriction, including food intake and food cravings.
Sleep restriction and its consequences are major public health problems, especially in older adults. Among the more severe physiological sequelae of sleep restriction is the development of insulin resistance. The mechanisms by which sleep restriction leads to increased insulin resistance are unknown, especially in vulnerable older adults; such research informs development of targeted interventions against the sleep loss/insulin resistance link. This study will administer drugs to clamp the function of each of these nodes to determine the regulatory changes that have occurred with sleep restriction. Even though the study is randomized order in design, the main comparison is before and after sleep restriction under each of these clamp conditions. Participants are admitted to the chronobiology laboratory where they are given 1 night of 10 hours sleep opportunity, followed by 4 nights of 4 hours sleep opportunity. Up to 40 participants can be enrolled. However, participants will be allowed an opportunity to be randomized to all 4 conditions so that as few as 10 participants may be required. We anticipate 5 men and 5 women will be enrolled assuming each undergoes all 4 clamp conditions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
5
Ketoconazole pill is taken 4 times per inpatient visit
Ganirelix subcutaneous injection is administered twice per inpatient visit
Dexamethasone pills is taken twice per inpatient visit
Los Angeles Biomedical Research Institute
Torrance, California, United States
Average Blood Cortisol Concentration
Cortisol is measured in blood every 10 minutes for a 5 hour period, at the beginning and at the end of 4 nights of sleep restriction. The average cortisol is the parameter of interest.
Time frame: 5 days
Average Blood Testosterone Concentration
Testosterone is measured in blood every 10 minutes for a 5 hour period, at the beginning and at the end of 4 nights of sleep restriction. The average cortisol is the parameter of interest.
Time frame: 5 days
Peak Blood Cortisol Concentration
This is the single maximal blood cortisol concentration that is measured during the entire 5 hour period, at the beginning and at the end of 4 nights of sleep restriction.
Time frame: 5 days
Peak Blood Testosterone Concentration
This is the single maximal blood testosterone concentration that is measured during the entire 5 hour period, at the beginning and at the end of 4 nights of sleep restriction.
Time frame: 5 days
Trough Blood Cortisol Concentration
This is the single minimal blood cortisol concentration that is measured during the entire 5 hour period, at the beginning and at the end of 4 nights of sleep restriction.
Time frame: 5 days
Trough Blood Testosterone Concentration
This is the single minimal blood testosterone concentration that is measured during the entire 5 hour period, at the beginning and at the end of 4 nights of sleep restriction.
Time frame: 5 days
Reaction time on Psychomotor Vigilance Task
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Dexamethasone IV injection is given twice per inpatient visit
Cosyntropin injection is given twice per inpatient visit
Recombinant Human Luteinizing Hormone is given as 6 IV infusion pulses per inpatient visit
Hydrocortisone IV push is given twice per inpatient visit
Gonadorelin IV injection is given twice per inpatient visit
Corticorelin IV injection is given twice per inpatient visit
Placebo for Ketoconazole are given 4 times per inpatient visit
Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per inpatient visit
Saline Solution (placebo) for ganirelix subcutaneous injection
This is measured by lapses in attention. As the person becomes more sleepy, there are more lapses (reaction time \>500 ms), at the beginning and at the end of 4 nights of sleep restriction.
Time frame: 5 days
Karolinska Sleepiness Scale
Measures how sleepy participants are using a scale of 1 (extremely alert) through 9. This scale will be used to assess changes in sleepiness throughout the day and through 4 nights of sleep restriction.
Time frame: 5 days
Two card gambling task
Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects participants' decision making. The end point is discriminability index, d'.
Time frame: 5 days
Modified Sternberg working memory test
Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects reaction time and accuracy.
Time frame: 5 days
Caloric Intake
The food given to participants is weighed. The amount that is not consumed is also weighed. The difference in weight is the amount of calories consumed.
Time frame: 5 days
Hunger
Hunger levels are assessed using the Flint visual analogue scale (VAS) to assess how 4 nights of sleep restriction affects participants' appetite.The Flint VAS asks the participant to rate 8 aspects of their hunger level on a scale from 1-5.
Time frame: 5 days
Food Cravings
Food cravings are measured using the Food Cravings Index (FCI) scale to assess which food groups each participant has cravings for and how their cravings change during 4 nights of sleep restriction. The participant ranks their craving for 33 food items on a scale from 1-5.
Time frame: 5 days