Sleep Restriction
Conditions
Keywords
testosterone, cortisol
Brief summary
The purpose of this study is to 1) determine how hypothalamic-pituitary-adrenal axis (HPA axis) activation occurs with sleep restriction 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.
Detailed description
Sleep restriction increases evening cortisol and decreases testosterone. These are the main catabolic and anabolic hormones in men, respectively. This catabolic-anabolic imbalance likely leads to metabolic and reproductive ill-health. The hypothalamic-pituitary-end organ (adrenal or testis) mechanisms that must underpin these changes are unknown. 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 80 participants (assuming twenty different participant for each of the 4 clamp conditions) can be enrolled. However, participants will be allowed an opportunity to be randomized to all 4 conditions so that as few as 20 participants may be required. Urn randomization will be used to ensure that 20 different participants are involved in each of the 4 conditions.
Interventions
Ketoconazole pill is taken 4 times per Inpatient Stay
DRUGGanirelix
Ganirelix subcutaneous injection is administered twice per Inpatient Stay
DRUGDexamethasone
Dexamethasone Pills is taken twice per Inpatient Stay
Dexamethasone IV injection is given twice per Inpatient Stay
cosyntropin injection is given twice per Inpatient Stay
DRUGRecombinant Human Luteinizing Hormone
Leutinizing-Releasing Hormone is given 6 IV infusion pulses per Inpatient Visit
DRUGHydrocortisone Injection
Hydrocortisone IV push is given twice per Inpatient Visit
DRUGGonadorelin
Gonadorelin IV injection is given twice per Inpatient Stay
DRUGCorticorelin
Corticorelin IV injection is given twice per Inpatient Stay
DRUGPlacebo oral capsule
Placebo for ketoconazole are given 4 times per Inpatient Stay
DRUGSaline Solution
Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per Inpatient Stay
Saline Solution (placebo) for ganirelix subcutaneous injection
Sponsors
Peter y. Liu
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
3 of the 4 conditions are masked by use of identical injections and pills. However one condition (adrenal testis) is not masked. Hence the study is partially masked.
Intervention model description
Blood is sampled every 10 minutes from 4PM to 9PM for future mathematical deconvolution in order to determine hormone pulse characteristics in response to the clamp conditions. These values are the primary endpoints.
Eligibility
Sex/Gender
MALE
Age
22 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Men aged 22-45 years * Willingness to provide written informed consent * Stable weight over preceding 6 weeks * Body Mass index (BMI) 20-28 kg/m2
Exclusion criteria
* Unable or unwilling to provide IRB (Internal Review Board)-approved informed consent * Clinical disorders and/or illnesses * Current medical or drug treatment, as assessed by questionnaire * History of brain injury or of learning disability - Vision or hearing impairment unless corrected back to normal * Anemia (Hct \<38%) * History of psychiatric illness * Clinically significant abnormalities in blood and urine, and free of traces of drugs * Other endocrine abnormalities including hypothyroidism or adrenal failure; primary gonadal disease as indicated by serum LH (luteinizing hormone) or FSH (follicle stimulating hormone) concentration \>10 or \>15 IU/L, respectively, hyperprolactinemia indicated by prolactin \>25ug/L * Type 2 Diabetes (HgbA1C) * Current smoker * Recent or concurrent drug or alcohol abuse * Blood donation in previous eight weeks * Travel across time zones within one month of entering the study * Sleep or circadian disorder * Shift work within three months of entering the study * Irregular bedtimes (not between 6 and 10 hours in duration) * Unoperated obstructive uropathy, recurrent prostatitis, indeterminate prostatic nodularity, Hx or Suspicion of cancer of the prostate gland or PSA (prostate-specific antigen) \>4ng/ml * Previous adverse reaction to sleep deprivation or any of the drugs to be administered * Concurrent participation in another research study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Blood Cortisol Concentration | 5 days | 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. |
| Average Blood Testosterone Concentration | 5 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Blood Cortisol Concentration | 5 days | 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. |
| Trough Blood Testosterone Concentration | 5 days | 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. |
| Reaction time on Psychomotor Vigilance Task | 5 days | 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. |
| Karolinska Sleepiness Scale | 5 days | 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. |
| Peak Blood Cortisol Concentration | 5 days | 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. |
| Modified Sternberg working memory test | 5 days | Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects reaction time and accuracy. |
| Caloric Intake | 5 days | 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. |
| Hunger Scale | 5 days | Hunger scale using Flint visual analogue scale to assess how 4 nights of sleep restriction affects participants' appetite. |
| Food Cravings | 5 days | Food cravings is measured using Food Cravings Index scale to assess which food groups participants have cravings for and how their cravings change during 4 nights of sleep restriction. |
| Two card gambling task | 5 days | Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects participants' decision making. The end point is discriminability index, d'. |
| Peak Blood Testosterone Concentration | 5 days | 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. |
Countries
United States
Outcome results
None listed