Hormonal Mechanisms of Sleep Restriction - Axis Study in Older Men and Postmenopausal Women

NCT04037605 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: P31056-01R
• Study Type: interventional
• Target: 5
• 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 and 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 (also known as Lutrepulse); Drug: Corticorelin (also known as Acthrel); Drug: Placebo oral tablet; 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 blood sample

Drug: Ganirelix; Drug: Dexamethasone injection; Drug: Gonadorelin (also known as Lutrepulse); Drug: Corticorelin (also known as Acthrel); Drug: Placebo oral tablet; Drug: Saline solution for injection

Pituitary Condition

EXPERIMENTAL

8 am - Saline Solution for Injection 10 am - Ketoconazole Pill 1 pm - Saline Solution for Injection 4 pm - Ketoconazole Pill \& start of hourly blood sampling 7 pm - GnRH and CRH 9 pm - Hydrocortisone Injection and last blood sample

Drug: Ketoconazole Pill (also known as nizoral); Drug: Hydrocortisone Injection (also known as solu-cortef); Drug: Gonadorelin (also known as Lutrepulse); Drug: Corticorelin (also known as Acthrel); Drug: Saline Solution

Adrenal/Testis Condition

EXPERIMENTAL

10 pm - Ganirelix Injection \& Dexamethasone Pills (night before) 8 am - Start of hourly blood sampling 10 am - Dexamethasone Pills 11 am - Last hourly blood sample taken 11:30 am - Start of blood sampling every 10 minutes 1 pm - Recombinant Human Luteinizing Hormone (rhLH) Injection 3 pm - rhLH Injection 5 pm - rhLH Injection 5 pm - Cosyntropin Injectable product 7 pm - GnRH and CRH Injections 9 pm - Last blood sample

Drug: Ganirelix; Drug: Dexamethasone Pill; Drug: Cosyntropin Injectable Product; Drug: Recombinant Human Luteinizing Hormone (also known as luveris); Drug: Gonadorelin (also known as Lutrepulse); Drug: Corticorelin (also known as Acthrel)

Interventions

Ketoconazole Pill (also known as nizoral) DRUG

Ketoconazole pill is taken 4 times per inpatient visit

Pituitary Condition

Ganirelix DRUG

Ganirelix subcutaneous injection is administered twice per inpatient visit

Adrenal/Testis Condition; Hypothalamic Condition

Dexamethasone Pill DRUG

Dexamethasone pills is taken twice per inpatient visit

Adrenal/Testis Condition

Dexamethasone injection DRUG

Dexamethasone IV injection is given twice per inpatient visit

Hypothalamic Condition

Cosyntropin Injectable Product DRUG

Cosyntropin injection is given twice per inpatient visit

Adrenal/Testis Condition

Recombinant Human Luteinizing Hormone (also known as luveris) DRUG

Recombinant Human Luteinizing Hormone is given as 6 IV infusion pulses per inpatient visit

Adrenal/Testis Condition

Hydrocortisone Injection (also known as solu-cortef) DRUG

Hydrocortisone IV push is given twice per inpatient visit

Pituitary Condition

Gonadorelin (also known as Lutrepulse) DRUG

Gonadorelin IV injection is given twice per inpatient visit

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

Corticorelin (also known as Acthrel) DRUG

Corticorelin IV injection is given twice per inpatient visit

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

Placebo oral tablet DRUG

Placebo for Ketoconazole are given 4 times per inpatient visit

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 visit

Control Condition; Pituitary Condition

Saline solution for injection DRUG

Saline Solution (placebo) for ganirelix subcutaneous injection

Control Condition; Hypothalamic Condition

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or postmenopausal women aged 60-80 years
• Willingness to provide written informed consent
• Stable weight over preceding 6 weeks
• Body Mass index (BMI) 22-28 kg/m2
• Physically and psychologically healthy
• Good habitual sleep with regular bedtimes
• Neither extreme morning- nor extreme evening-type using Horne-Ostberg Morningness-Eveningness criteria

You may not qualify if:

• Medications that interfere with the adrenal or gonadal axis will be excluded
• 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

Sponsors & Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: 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: early 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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Blood is sampled every 10 minutes from 4 pm to 9 pm for future mathematical deconvolution in order to determine hormone pulse characteristics in response to the clamp conditions.

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: July 30, 2019
• Study Start: February 9, 2020
• Primary Completion: July 24, 2022
• Study Completion (Estimated): June 24, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)