Recruiting

Cortisol Impact

Sponsor:

Washington State University

Code:

NCT07494084

Conditions

Shift Work Schedule

Circadian Rhythm

Insulin Resistance

Circadian Misalignment

Eligibility Criteria

Sex: All

Age: 18 - 45

Healthy Volunteers: Accepted

Interventions

Metyrapone And Hydrocortisone

Dextrose

insulin

Study Details

Brief summary:

The purpose of this study is to examine the impact of timed cortisol release or differently timed cortisol rhythms on insulin resistance in both men and women undergoing sleep restriction. Chronic sleep loss is highly prevalent, affecting 1 in 3 adults in the US. Chronic sleep loss causes stress which induces insulin resistance and leads to obesity and type 2 diabetes. Many factors contribute to sleep loss including shift work, environmental disturbances, sleep/circadian disorders and comorbid medical and mental health conditions. Sleep loss increases the stress hormone cortisol in the evening and decreases daytime testosterone. Examining these hormones in a controlled laboratory environment under different sleep schedules may help researchers find solutions for adults experiencing negative health consequences related to chronic sleep loss.

Conditions

Shift Work Schedule

Circadian Rhythm

Insulin Resistance

Circadian Misalignment

Study ID

NCT07494084

Start date

Jul 16, 2026

Status verified date

Sep, 2026

Completion date

Jul, 2029

Anticipated

Primary completion date

Mar, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 45

Healthy Volunteers: Accepted

Inclusion Criteria:

1. Must be between 18-45 years old.
2. Has a BMI of 18-25 kg/m2 stable weight over the previous 6 weeks.
3. Is physically and psychologically healthy (incl. regular menstrual cycles in women, no clinical disorders and/or illnesses). Women will be studied during the follicular phase of their menstrual cycle.

Menstrual cycle criteria (using PMID 10941950) 18 to 25 years - Cycle variation ≤9 days 26 to 41 years - Cycle variation ≤7 days 42 to 45 years - Cycle variation ≤9 days
4. No current medical or drug treatment (to include steroids or hormones of any type including contraceptives), as assessed by questionnaire.
5. Has a negative pregnancy test (women), no clinically significant abnormalities in blood and urine, and free of traces of drugs.
6. No history of clinically relevant psychiatric illness.
7. No previous history of drug or alcohol abuse.
8. Not a current smoker.
9. No history of brain injury or of learning disability.
10. No previous adverse reaction to sleep deprivation, jet lag, shift work or any of the drugs to be administered.
11. Not vision or hearing impairment unless corrected back to normal.
12. No endocrine disorder (no abnormal thyroid function tests; no abnormal morning blood cortisol; no primary gonadal disease as indicated by serum LH or FSH concentration > 10 or > 15 IU/L, respectively; and no hyperprolactinemia indicated by prolactin > 25 μg/L).
13. No sleep or circadian disorder.
14. Has good habitual sleep with regular bedtimes (between 6 and 10 hours in duration).
15. Not extreme morning- nor extreme evening-type using Horne-Ostberg Morningness-Eveningness criteria.
16. No travel across time zones within one month of entering the study.
17. No shift work within three months of entering the study.
18. No anemia (hematocrit <38% in men, <34% in women).
19. No blood donation within the previous 8 weeks.
20. No concurrent participation in another research study.

Study Design

Enrollment

48 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Diagnostic

Interventions and Outcome Measures

Arms

active comparator: Misaligned cortisol rhythm-night shift condition

Cortisol will be clamped with oral administration of Metyrapone, which blocks endogenous cortisol biosynthesis. A loading dose of 3,000mg will be given at 10:00 on day 2. Every 4 hours throughout the sleep restriction and sleep deprivation phases, 500mg will be administered beginning at 14:00 on day 2 and ending with a dose at 18:00 on day 5.

Using a subcutaneous pump, hydrocortisone is administered here as physiological replacement, with pulses every 3 hours beginning at 10:00 on day 2.

Participants assigned to the misaligned cortisol rhythm condition will receive: lowest doses (0.5mg) at 22:00 and 01:00; moderate doses (2.3mg) at 13:00, 16:00, and 19:00; and highest doses (4.0mg) at 04:00, 07:00, and 10:00. An oral 25mg dose of hydrocortisone will be given at the end of the constant routine period to prevent any future hypocortisolemia associated with the hormone clamp.

active comparator: Realigned cortisol rhythm-night shift condition

Cortisol will be clamped with oral administration of Metyrapone, which blocks endogenous cortisol biosynthesis. A loading dose of 3,000mg will be given at 10:00 on day 2. Every 4 hours throughout the sleep restriction and sleep deprivation phases. Participants will receive their doses at a 12-hour offset from the misaligned condition, with: lowest doses (0.5mg) at 10:00 and 13:00; moderate doses (2.3mg) at 01:00, 04:00, and 07:00; and highest doses (4.0mg) at 16:00, 19:00, and 22:00. The last subcutaneous dose will be administered at 19:00 on day 5. An oral 25mg dose of hydrocortisone will be given at the end of the constant routine period to prevent any future hypocortisolemia associated with the hormone clamp.

active comparator: Fixed cortisol shape condition- day shift condition

Cortisol will be clamped with oral administration of Metyrapone, which blocks endogenous cortisol biosynthesis. A loading dose of 3,000mg will be given at 10:00 on day 2. Every 4 hours throughout the sleep restriction and sleep deprivation phases, 500mg will be administered beginning at 14:00 on day 2 and ending with a dose at 06:00 on day 5. Using a subcutaneous pump, hydrocortisone is administered here as physiological replacement, with pulses every 3 hours beginning at 10:00 on day 2. Participants assigned to the fixed cortisol shape condition will receive: lowest doses (0.5mg) at 22:00 and 01:00; moderate doses (2.3mg) at 13:00, 16:00, and 19:00; and highest doses (4.0mg) at 04:00, 07:00, and 10:00. The last subcutaneous dose will be administered at 07:00 on day 5. An oral 25mg dose of hydrocortisone will be given at the end of the constant routine period to prevent any future hypocortisolemia associated with the hormone clamp.

placebo comparator: Unfixed cortisol shape condition-day shift condition

Participants will receive a metyrapone placebo at times matching the doses in Condition A (i.e., at 10:00 on day 2 and continuing every 4 hours until 06:00 on day 5). Using a subcutaneous pump, placebo hydrocortisone is administered matching the doses in Condition A (i.e., with pulses every 3 hours beginning at 10:00 on day 2 until 07:00 on day 5). A placebo matching the oral hydrocortisone will be administered at 10:00 on day 5.

Interventions

Metyrapone And Hydrocortisone

Cortisol will be clamped with oral administration of Metyrapone, which blocks endogenous cortisol biosynthesis. A loading dose of 3,000mg will be given at 10:00 on day 2. Every 4 hours throughout the sleep restriction and sleep deprivation phases, 500mg will be administered beginning at 14:00 on day 2 and ending with a dose at 18:00 on day 5.

Using a subcutaneous pump, hydrocortisone is administered here as physiological replacement, with pulses every 3 hours beginning at 10:00 on day 2. Participants will receive 3 tiers of doses: low (0.5mg), moderate (2.3mg) and high (4.0mg), the timing of which is specified by their condition assignment. For all participants, an oral 25mg dose of hydrocortisone will be given at the end of the constant routine period to prevent any future hypocortisolemia associated with the hormone clamp.

Dextrose

The frequently sampled intravenous glucose tolerance test is performed before and after sleep restriction, and is widely used and validated. This procedure requires intravenous administration of dextrose, 300 mg/kg as a bolus at time zero. Insulin (0.03 units/kg/min) will be slowly infused intravenously over a 5 minute period from 20 to 25 minutes. Few side effects are anticipated as both doses of glucose and insulin should result in a high, but physiological peak. Administration of insulin as 5-min infusion for clinical studies (rather than bolus) reduces the max concentrations achieved. It is not uncommon for glucose to dip below fasting glycemia at some point after the insulin administration. The concentration at the nadir depends on the subject's insulin sensitivity. Return to fasting level is a function of the waning of the insulin effect (incorporated into the minimal model) as well as counterregulation (which depends on the concentration at the nadir). This can be addressed,

insulin

The frequently sampled intravenous glucose tolerance test is performed before and after sleep restriction, and is widely used and validated. This procedure requires intravenous administration of dextrose, 300 mg/kg as a bolus at time zero. Insulin (0.03 units/kg/min) will be slowly infused intravenously over a 5 minute period from 20 to 25 minutes. Few side effects are anticipated as both doses of glucose and insulin should result in a high, but physiological peak. Administration of insulin as 5-min infusion for clinical studies (rather than bolus) reduces the max concentrations achieved. It is not uncommon for glucose to dip below fasting glycemia at some point after the insulin administration. The concentration at the nadir depends on the subject's insulin sensitivity. Return to fasting level is a function of the waning of the insulin effect (incorporated into the minimal model) as well as counterregulation (which depends on the concentration at the nadir). This can be addressed,

Primary outcome measure

  • Insulin resistance-Minimal Model (Si) [ Time Frame: Change from baseline collection. ]
  • Insulin Resistance-Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: Change from baseline collection. ]
  • Insulin Resistance-Insulin Sensitivity Index (Mi) [ Time Frame: Change from baseline collection. ]

Central Contacts and Locations

Central contacts

Devon A Hansen, PhD

509-358-7754devon.hansen@wsu.edu

Olivia Brooks, MS

509-358-7904olivia.brooks@wsu.edu

Locations

Sleep and Performance Research Center

Recruiting

Spokane, Washington, United States, 99202

Contacts

Olivia Brooks, MS

509-358-7750olivia.brooks@wsu.edu

Devon Hansen, PhD

509-358-7754devon.hansen@wsu.edu

Principal Investigator:

Hans Van Dongen, PhD

More Information

Sponsor

Washington State University

Last update posted

Sep 18, 2026

Last verified

Sep, 2026

Keywords

  • Shift work
  • insulin resistance
  • sleep
  • circadian rhythm
  • type 2 diabetes

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-24. This information was provided to ClinicalTrials.gov by Washington State University on 2026-09-18. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.