Hormonal Mechanisms of Sleep Restriction - Axis Study

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Torrance, California, United States, 90509
        • Los Angeles Biomedical Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

22 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Control Condition

8 am - Saline Solution for Injection 10 am - Placebo oral capsule

1 pm - Saline Solution for Injection 4 pm - Placebo oral capsule & start hourly blood sampling 7 pm - Gonadorelin (GnRH) and Corticorelin (CRH) injections 9 pm - Saline Solution for Injection & last blood sample

Gonadorelin IV injection is given twice per Inpatient Stay
Other Names:
  • Lutrepulse
Corticorelin IV injection is given twice per Inpatient Stay
Other Names:
  • Acthrel
Placebo for ketoconazole are given 4 times per Inpatient Stay
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
Experimental: Hypothalamic Condition

8 am - Ganirelix 10 am - Placebo oral capsule

1 pm - Dexamethasone injection 4 pm - Placebo oral capsule and start of hourly blood sampling 7 pm - GnRH and CRH injections 9 pm - Saline Solution for Injection and last sample of blood taken

Gonadorelin IV injection is given twice per Inpatient Stay
Other Names:
  • Lutrepulse
Corticorelin IV injection is given twice per Inpatient Stay
Other Names:
  • Acthrel
Placebo for ketoconazole are given 4 times per Inpatient Stay
Saline Solution (placebo) for ganirelix subcutaneous injection
Ganirelix subcutaneous injection is administered twice per Inpatient Stay
Dexamethasone IV injection is given twice per Inpatient Stay
Experimental: Pituitary Condition

8am - Saline Solution for Injection 10am - Ketoconazole Pill

1pm - Saline Solution for Injection 4pm - Ketoconazole Pill & start of hourly blood sampling 7pm - GnRH and CRH 9pm - Hydrocortisone Injection & last blood sample

Gonadorelin IV injection is given twice per Inpatient Stay
Other Names:
  • Lutrepulse
Corticorelin IV injection is given twice per Inpatient Stay
Other Names:
  • Acthrel
Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per Inpatient Stay
Ketoconazole pill is taken 4 times per Inpatient Stay
Other Names:
  • Nizoral
Hydrocortisone IV push is given twice per Inpatient Visit
Other Names:
  • solu-cortef
Experimental: Adrenal/Testis Condition

10pm - Ganirelix Injection & Dexamethasone Pills (night before) 8am - start of hourly blood sampling 10am - Dexamethasone Pills 11am - last hourly blood sample taken 11:30am - start of blood sampling every 10 minutes

1pm - Recombinant Human Luteinizing Hormone (rhLH) Injection 3pm - rhLH Injection 5pm - rhLH Injection 5pm - Cosyntropin Injectable product 7pm - GnRH and CRH Injections 9pm - last blood sample taken

Gonadorelin IV injection is given twice per Inpatient Stay
Other Names:
  • Lutrepulse
Corticorelin IV injection is given twice per Inpatient Stay
Other Names:
  • Acthrel
Ganirelix subcutaneous injection is administered twice per Inpatient Stay
Dexamethasone Pills is taken twice per Inpatient Stay
cosyntropin injection is given twice per Inpatient Stay
Leutinizing-Releasing Hormone is given 6 IV infusion pulses per Inpatient Visit
Other Names:
  • Luveris

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Average Blood Cortisol Concentration
Time Frame: 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.
5 days
Average Blood Testosterone Concentration
Time Frame: 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.
5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Blood Cortisol Concentration
Time Frame: 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.
5 days
Peak Blood Testosterone Concentration
Time Frame: 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.
5 days
Trough Blood Cortisol Concentration
Time Frame: 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.
5 days
Trough Blood Testosterone Concentration
Time Frame: 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.
5 days
Reaction time on Psychomotor Vigilance Task
Time Frame: 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.
5 days
Karolinska Sleepiness Scale
Time Frame: 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.
5 days
Two card gambling task
Time Frame: 5 days
Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects participants' decision making. The end point is discriminability index, d'.
5 days
Modified Sternberg working memory test
Time Frame: 5 days
Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects reaction time and accuracy.
5 days
Caloric Intake
Time Frame: 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.
5 days
Hunger Scale
Time Frame: 5 days
Hunger scale using Flint visual analogue scale to assess how 4 nights of sleep restriction affects participants' appetite.
5 days
Food Cravings
Time Frame: 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.
5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Peter Liu, MD, PhD, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 8, 2017

Primary Completion (Actual)

October 30, 2020

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

April 11, 2017

First Submitted That Met QC Criteria

May 3, 2017

First Posted (Actual)

May 8, 2017

Study Record Updates

Last Update Posted (Estimated)

January 26, 2024

Last Update Submitted That Met QC Criteria

January 24, 2024

Last Verified

January 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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