Sleep RestrictionPhase 1NCT03142893
Hormonal Mechanisms of Sleep Restriction - Axis Study
A Phase 1 study testing Ketoconazole Pill, Ganirelix and Dexamethasone in people with Sleep Restriction, run by Peter y. Liu at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Sleep Restriction
- What is being tested?
- Ketoconazole Pill, Ganirelix and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2017to 30 Jun 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Los Angeles Biomedical Research Institute
Torrance, California, 90509
About this 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.
Read the 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.
- Conditions
- Sleep Restriction
- Being tested
- Ketoconazole Pill, Ganirelix, Dexamethasone, Dexamethasone Injection, Cosyntropin Injectable Product
- Keywords
- testosterone, cortisol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketoconazole PillDrug
Also called Nizoral
Ketoconazole pill is taken 4 times per Inpatient Stay
GanirelixDrug
Ganirelix subcutaneous injection is administered twice per Inpatient Stay
DexamethasoneDrug
Dexamethasone Pills is taken twice per Inpatient Stay
Dexamethasone InjectionDrug
Dexamethasone IV injection is given twice per Inpatient Stay
Cosyntropin Injectable ProductDrug
cosyntropin injection is given twice per Inpatient Stay
Recombinant Human Luteinizing HormoneDrug
Also called Luveris
Leutinizing-Releasing Hormone is given 6 IV infusion pulses per Inpatient Visit
Hydrocortisone InjectionDrug
Also called solu-cortef
Hydrocortisone IV push is given twice per Inpatient Visit
GonadorelinDrug
Also called Lutrepulse
Gonadorelin IV injection is given twice per Inpatient Stay
CorticorelinDrug
Also called Acthrel
Corticorelin IV injection is given twice per Inpatient Stay
Placebo oral capsuleDrug
Placebo for ketoconazole are given 4 times per Inpatient Stay
Saline SolutionDrug
Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per Inpatient Stay
Saline Solution for InjectionDrug
Saline Solution (placebo) for ganirelix subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Ganirelix; Drug: Dexamethasone; Drug: Cosyntropin Injectable Product; Drug: Recombinant Human Luteinizing Hormone; Drug: Gonadorelin; Drug: Corticorelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 5 days
Secondary outcomes (11)
Peak Blood Cortisol Concentration
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.
Measured: 5 days
Peak Blood Testosterone Concentration
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.
Measured: 5 days
Trough Blood Cortisol Concentration
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.
Measured: 5 days
Trough Blood Testosterone Concentration
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.
Measured: 5 days
Reaction time on Psychomotor Vigilance Task
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.
Measured: 5 days
Karolinska Sleepiness Scale
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.
Measured: 5 days
Two card gambling task
Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects participants' decision making. The end point is discriminability index, d'.
Measured: 5 days
Modified Sternberg working memory test
Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects reaction time and accuracy.
Measured: 5 days
Caloric Intake
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.
Measured: 5 days
Hunger Scale
Hunger scale using Flint visual analogue scale to assess how 4 nights of sleep restriction affects participants' appetite.
Measured: 5 days
Food Cravings
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.
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2017
- Study start8 May 2017
- Primary completion30 Oct 2020
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep RestrictionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peter y. Liu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Peter y. Liu, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Investigators
- Peter Liu, MD, PhD, Principal investigator, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03142893
- Sponsor's protocol ID
- 30068-01A
- Status last verified
- Sep 2025
- First submitted
- 11 Apr 2017
- Last updated
- 11 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hormonal Mechanisms of Sleep Restriction - Axis Study
- ClinicalTrials.gov ID
- NCT03142893
- Acronym / sponsor ID
- 30068-01A
- Conditions
- Sleep Restriction
- Keywords
- testosterone, cortisol
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Peter y. LiuUniversity, hospital or other
- Study start
- 8 May 2017 (actual)
- Primary completion
- 30 Oct 2020 (actual)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 8 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Control Condition | Experimental | Drug: Gonadorelin, Drug: Corticorelin, Drug: Placebo oral capsule, Drug: Saline Solution, Drug: Saline Solution for Injection8 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 |
| Hypothalamic Condition | Experimental | Drug: Ganirelix, Drug: Dexamethasone Injection, Drug: Gonadorelin, Drug: Corticorelin, Drug: Placebo oral capsule, Drug: Saline Solution for Injection8 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 |
| Pituitary Condition | Experimental | Drug: Ketoconazole Pill, Drug: Hydrocortisone Injection, Drug: Gonadorelin, Drug: Corticorelin, Drug: Saline Solution8am - 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 |
| Adrenal/Testis Condition | Experimental | Drug: Ganirelix, Drug: Dexamethasone, Drug: Cosyntropin Injectable Product, Drug: Recombinant Human Luteinizing Hormone, Drug: Gonadorelin, Drug: Corticorelin10pm - 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 |
Who may qualify
- Ages
- 22 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (19 listed)
- 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%)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketoconazole PillAlso: NizoralKetoconazole pill is taken 4 times per Inpatient Stay | Drug | Pituitary Condition |
| GanirelixGanirelix subcutaneous injection is administered twice per Inpatient Stay | Drug | Adrenal/Testis Condition, Hypothalamic Condition |
| DexamethasoneDexamethasone Pills is taken twice per Inpatient Stay | Drug | Adrenal/Testis Condition |
| Dexamethasone InjectionDexamethasone IV injection is given twice per Inpatient Stay | Drug | Hypothalamic Condition |
| Cosyntropin Injectable Productcosyntropin injection is given twice per Inpatient Stay | Drug | Adrenal/Testis Condition |
| Recombinant Human Luteinizing HormoneAlso: LuverisLeutinizing-Releasing Hormone is given 6 IV infusion pulses per Inpatient Visit | Drug | Adrenal/Testis Condition |
| Hydrocortisone InjectionAlso: solu-cortefHydrocortisone IV push is given twice per Inpatient Visit | Drug | Pituitary Condition |
| GonadorelinAlso: LutrepulseGonadorelin IV injection is given twice per Inpatient Stay | Drug | Adrenal/Testis Condition, Control Condition, Hypothalamic Condition, Pituitary Condition |
| CorticorelinAlso: ActhrelCorticorelin IV injection is given twice per Inpatient Stay | Drug | Adrenal/Testis Condition, Control Condition, Hypothalamic Condition, Pituitary Condition |
| Placebo oral capsulePlacebo for ketoconazole are given 4 times per Inpatient Stay | Drug | Control Condition, Hypothalamic Condition |
| Saline SolutionSaline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per Inpatient Stay | Drug | Control Condition, Pituitary Condition |
| Saline Solution for InjectionSaline Solution (placebo) for ganirelix subcutaneous injection | Drug | Control Condition, Hypothalamic Condition |
Primary outcome
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.
11 secondary outcomes
Peak Blood Cortisol Concentration
Time frame: 5 days
Peak Blood Testosterone Concentration
Time frame: 5 days
Trough Blood Cortisol Concentration
Time frame: 5 days
Trough Blood Testosterone Concentration
Time frame: 5 days
Reaction time on Psychomotor Vigilance Task
Time frame: 5 days
Karolinska Sleepiness Scale
Time frame: 5 days
Two card gambling task
Time frame: 5 days
Modified Sternberg working memory test
Time frame: 5 days
Caloric Intake
Time frame: 5 days
Hunger Scale
Time frame: 5 days
Food Cravings
Time frame: 5 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Liu, MD, PhD principal investigator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketoconazole Pill, Ganirelix and Dexamethasone in people with Sleep Restriction, run by Peter y. Liu at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Blood Cortisol Concentration (time frame: 5 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.