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Hormonal Mechanisms of Sleep Restriction - Axis Study

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ClinicalTrials.gov Identifier: NCT03142893
Recruitment Status : Recruiting
First Posted : May 8, 2017
Last Update Posted : August 7, 2018
Sponsor:
Information provided by (Responsible Party):
Los Angeles Biomedical Research Institute

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.

Condition or disease Intervention/treatment Phase
Sleep Restriction Drug: Ketoconazole Pill Drug: Ganirelix Drug: Dexamethasone Drug: Dexamethasone Injection Drug: Cosyntropin Injectable Product Drug: Recombinant Human Luteinizing Hormone Drug: Hydrocortisone Injection Drug: Gonadorelin Drug: Corticorelin Drug: Placebo oral capsule Drug: Saline Solution Drug: Saline Solution for Injection Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
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
Official Title: Hormonal Mechanisms of Sleep Restriction - Axis Study
Actual Study Start Date : May 8, 2017
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : May 1, 2020

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

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

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

Drug: Ganirelix
Ganirelix subcutaneous injection is administered twice per Inpatient Stay

Drug: Dexamethasone Injection
Dexamethasone IV injection is given twice per Inpatient Stay

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 for Injection
Saline Solution (placebo) for ganirelix subcutaneous 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

Drug: Ketoconazole Pill
Ketoconazole pill is taken 4 times per Inpatient Stay
Other Name: Nizoral

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: Saline Solution
Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per Inpatient Stay

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

Drug: Ganirelix
Ganirelix subcutaneous injection is administered twice per Inpatient Stay

Drug: Dexamethasone
Dexamethasone Pills is taken 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: 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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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. 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.

  6. 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.

  7. 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'.

  8. 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.

  9. 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.

  10. Hunger Scale [ Time Frame: 5 days ]
    Hunger scale using Flint visual analogue scale to assess how 4 nights of sleep restriction affects participants' appetite.

  11. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   22 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03142893


Contacts
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Contact: Peter Liu, MD, PhD 310-222-1867 pliu@labiomed.org

Locations
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United States, California
Los Angeles Biomedical Research Institute Recruiting
Torrance, California, United States, 90509
Contact: Megumi Yokomizo, BA    310-222-1860    myokomizo@labiomed.org   
Principal Investigator: Peter Y Liu, MD PhD         
Sponsors and Collaborators
Los Angeles Biomedical Research Institute
Investigators
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Principal Investigator: Peter Liu, MD, PhD Los Angeles Biomedical Research Institute

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Responsible Party: Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier: NCT03142893     History of Changes
Other Study ID Numbers: 30068-01A
First Posted: May 8, 2017    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Los Angeles Biomedical Research Institute:
testosterone
cortisol

Additional relevant MeSH terms:
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Pharmaceutical Solutions
Dexamethasone
Dexamethasone acetate
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Hormones
Cosyntropin
Corticotropin-Releasing Hormone
Prolactin Release-Inhibiting Factors
BB 1101
Ketoconazole
Ganirelix
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors