Hormonal Mechanisms of Sleep Restriction - Axis Study

Sleep Restriction Clinical Trial

Official title:

Hormonal Mechanisms of Sleep Restriction - Axis Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03142893
• Other study ID #: 30068-01A
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 8, 2017
• Est. completion date: March 31, 2025

Study information

• Verified date: March 2024
• Source: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: March 31, 2025
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 22 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Sleep Restriction

Intervention

Drug:
• Ketoconazole Pill
Ketoconazole pill is taken 4 times per Inpatient Stay
• Ganirelix
Ganirelix subcutaneous injection is administered twice per Inpatient Stay
• Dexamethasone
Dexamethasone Pills is taken twice per Inpatient Stay
• Dexamethasone Injection
Dexamethasone IV injection is given twice per Inpatient Stay
• Cosyntropin Injectable Product
cosyntropin injection is given twice per Inpatient Stay
• Recombinant Human Luteinizing Hormone
Leutinizing-Releasing Hormone is given 6 IV infusion pulses per Inpatient Visit
• Hydrocortisone Injection
Hydrocortisone IV push is given twice per Inpatient Visit
• Gonadorelin
Gonadorelin IV injection is given twice per Inpatient Stay
• Corticorelin
Corticorelin IV injection is given twice per Inpatient Stay
• Placebo oral capsule
Placebo for ketoconazole are given 4 times per Inpatient Stay
• Saline Solution
Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per Inpatient Stay
• Saline Solution for Injection
Saline Solution (placebo) for ganirelix subcutaneous injection

Locations

Country	Name	City	State
United States	Los Angeles Biomedical Research Institute	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	5 days
Primary	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.	5 days
Secondary	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.	5 days
Secondary	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.	5 days
Secondary	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.	5 days
Secondary	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.	5 days
Secondary	Reaction time on Psychomotor Vigilance Task	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.	5 days
Secondary	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.	5 days
Secondary	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'.	5 days
Secondary	Modified Sternberg working memory test	Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects reaction time and accuracy.	5 days
Secondary	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.	5 days
Secondary	Hunger Scale	Hunger scale using Flint visual analogue scale to assess how 4 nights of sleep restriction affects participants' appetite.	5 days
Secondary	Food Cravings	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.	5 days