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Hormonal Mechanisms of Sleep Restriction - Axis Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03142893
Recruitment Status : Active, not recruiting
First Posted : May 8, 2017
Last Update Posted : March 15, 2022
Sponsor:
Information provided by (Responsible Party):
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Tracking Information
First Submitted Date  ICMJE April 11, 2017
First Posted Date  ICMJE May 8, 2017
Last Update Posted Date March 15, 2022
Actual Study Start Date  ICMJE May 8, 2017
Actual Primary Completion Date October 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2017)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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'.
  • 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.
  • 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.
  • Hunger Scale [ Time Frame: 5 days ]
    Hunger scale using Flint visual analogue scale to assess how 4 nights of sleep restriction affects participants' appetite.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hormonal Mechanisms of Sleep Restriction - Axis Study
Official Title  ICMJE Hormonal Mechanisms of Sleep Restriction - Axis Study
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Triple (Participant, 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.
Primary Purpose: Basic Science
Condition  ICMJE Sleep Restriction
Intervention  ICMJE
  • Drug: Ketoconazole Pill
    Ketoconazole pill is taken 4 times per Inpatient Stay
    Other Name: Nizoral
  • Drug: Ganirelix
    Ganirelix subcutaneous injection is administered twice per Inpatient Stay
  • Drug: Dexamethasone
    Dexamethasone Pills is taken twice per Inpatient Stay
  • Drug: Dexamethasone Injection
    Dexamethasone IV injection is given twice per Inpatient Stay
  • Drug: Cosyntropin Injectable Product
    cosyntropin injection is given twice per Inpatient Stay
  • Drug: Recombinant Human Luteinizing Hormone
    Leutinizing-Releasing Hormone is given 6 IV infusion pulses per Inpatient Visit
    Other Name: Luveris
  • Drug: Hydrocortisone Injection
    Hydrocortisone IV push is given twice per Inpatient Visit
    Other Name: solu-cortef
  • Drug: Gonadorelin
    Gonadorelin IV injection is given twice per Inpatient Stay
    Other Name: Lutrepulse
  • Drug: Corticorelin
    Corticorelin IV injection is given twice per Inpatient Stay
    Other Name: Acthrel
  • Drug: Placebo oral capsule
    Placebo for ketoconazole are given 4 times per Inpatient Stay
  • Drug: Saline Solution
    Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per Inpatient Stay
  • Drug: Saline Solution for Injection
    Saline Solution (placebo) for ganirelix subcutaneous injection
Study Arms  ICMJE
  • 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

    Interventions:
    • Drug: Gonadorelin
    • Drug: Corticorelin
    • Drug: Placebo oral capsule
    • Drug: Saline Solution
    • Drug: Saline Solution for 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

    Interventions:
    • Drug: Ganirelix
    • Drug: Dexamethasone Injection
    • Drug: Gonadorelin
    • Drug: Corticorelin
    • Drug: Placebo oral capsule
    • Drug: Saline Solution for Injection
  • 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

    Interventions:
    • Drug: Ketoconazole Pill
    • Drug: Hydrocortisone Injection
    • Drug: Gonadorelin
    • Drug: Corticorelin
    • Drug: Saline Solution
  • 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

    Interventions:
    • Drug: Ganirelix
    • Drug: Dexamethasone
    • Drug: Cosyntropin Injectable Product
    • Drug: Recombinant Human Luteinizing Hormone
    • Drug: Gonadorelin
    • Drug: Corticorelin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2017)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2022
Actual Primary Completion Date October 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 22 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03142893
Other Study ID Numbers  ICMJE 30068-01A
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter Liu, MD, PhD Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
PRS Account Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP