Hormonal Mechanisms of Sleep Restriction - Axis Study

NCT03142893 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 30068-01A
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Sleep Restriction

Keywords

testosterone; cortisol

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (11)

• Peak Blood Cortisol Concentration

  5 days

• Peak Blood Testosterone Concentration

  5 days

• Trough Blood Cortisol Concentration

  5 days

• Trough Blood Testosterone Concentration

  5 days

• Reaction time on Psychomotor Vigilance Task

  5 days

Study Arms (4)

Control Condition

EXPERIMENTAL

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; Drug: Corticorelin; Drug: Placebo oral capsule; Drug: Saline Solution; Drug: Saline Solution for Injection

Hypothalamic Condition

EXPERIMENTAL

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; Drug: Dexamethasone Injection; Drug: Gonadorelin; Drug: Corticorelin; Drug: Placebo oral capsule; Drug: Saline Solution for Injection

Pituitary Condition

EXPERIMENTAL

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; Drug: Hydrocortisone Injection; Drug: Gonadorelin; Drug: Corticorelin; Drug: Saline Solution

Adrenal/Testis Condition

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Cosyntropin Injectable Product; Drug: Recombinant Human Luteinizing Hormone; Drug: Gonadorelin; Drug: Corticorelin

Interventions

Ketoconazole Pill DRUG

Ketoconazole pill is taken 4 times per Inpatient Stay

Also known as: Nizoral

Pituitary Condition

Ganirelix DRUG

Ganirelix subcutaneous injection is administered twice per Inpatient Stay

Adrenal/Testis Condition; Hypothalamic Condition

Dexamethasone DRUG

Dexamethasone Pills is taken twice per Inpatient Stay

Adrenal/Testis Condition

Dexamethasone Injection DRUG

Dexamethasone IV injection is given twice per Inpatient Stay

Hypothalamic Condition

Cosyntropin Injectable Product DRUG

cosyntropin injection is given twice per Inpatient Stay

Adrenal/Testis Condition

Recombinant Human Luteinizing Hormone DRUG

Leutinizing-Releasing Hormone is given 6 IV infusion pulses per Inpatient Visit

Also known as: Luveris

Adrenal/Testis Condition

Hydrocortisone Injection DRUG

Hydrocortisone IV push is given twice per Inpatient Visit

Also known as: solu-cortef

Pituitary Condition

Gonadorelin DRUG

Gonadorelin IV injection is given twice per Inpatient Stay

Also known as: Lutrepulse

Adrenal/Testis Condition; Control Condition; Hypothalamic Condition; Pituitary Condition

Corticorelin DRUG

Corticorelin IV injection is given twice per Inpatient Stay

Also known as: Acthrel

Adrenal/Testis Condition; Control Condition; Hypothalamic Condition; Pituitary Condition

Placebo oral capsule DRUG

Placebo for ketoconazole are given 4 times per Inpatient Stay

Control Condition; Hypothalamic Condition

Saline Solution DRUG

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

Control Condition; Pituitary Condition

Saline Solution for Injection DRUG

Saline Solution (placebo) for ganirelix subcutaneous injection

Control Condition; Hypothalamic Condition

Eligibility Criteria

• Age: 22 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peter y. Liu: lead

Study Sites (1)

Los Angeles Biomedical Research Institute

Torrance, California, 90509, United States

Location

MeSH Terms

Interventions

Ketoconazole; ganirelix; Dexamethasone; Calcium Dobesilate; Luteinizing Hormone, beta Subunit; Hydrocortisone; hydrocortisone hemisuccinate; Gonadotropin-Releasing Hormone; Corticotropin-Releasing Hormone; corticorelin ovine; Saline Solution; Injections

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Luteinizing Hormone; Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Neuropeptides; Oligopeptides; Nerve Tissue Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Peter Liu, MD, PhD

  Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: May 8, 2017
• Study Start: May 8, 2017
• Primary Completion: October 30, 2020
• Study Completion (Estimated): June 30, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)