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Sleep Loss and Circadian Misalignment - Mechanisms of Insulin Resistance

ClinicalTrials.gov IDNCT07494084

PhasePHASE4

Enrollment48

SponsorWashington State University

Age18 Years

SexALL

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Conditions studied

Shift Work Schedule, Circadian Rhythm, Insulin Resistance, Circadian Misalignment

About this study

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.

Interventions

Drug: 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.
Drug: 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,
Drug: 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 outcomes

Insulin resistance-Minimal Model (Si) (Change from baseline collection.)
Insulin Resistance-Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (Change from baseline collection.)
Insulin Resistance-Insulin Sensitivity Index (Mi) (Change from baseline collection.)

Eligibility information

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 locations

Sleep and Performance Research Center, Spokane, Washington 99202 United States

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.