Sleep Loss for Insulin Resistance
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores how different patterns of the stress hormone cortisol might affect insulin resistance, a condition where the body doesn't use insulin well, leading to high blood sugar, in people who don't get enough sleep. Researchers use two drugs, metyrapone and hydrocortisone, to control cortisol release while participants follow various sleep schedules. The goal is to understand how cortisol impacts health issues like obesity and type 2 diabetes, which link to chronic sleep loss. This trial might suit healthy adults who regularly experience sleep disruptions due to shift work or other factors. As a Phase 4 trial, the treatment has already received FDA approval and proven effective, helping to understand how it benefits more patients.
Will I have to stop taking my current medications?
Yes, you must not be on any current medical or drug treatment, including steroids or hormones like contraceptives, to participate in this trial.
What is the safety track record for Metyrapone and Hydrocortisone?
Research has shown that metyrapone, one of the treatments in this study, is usually well-tolerated by adults. A study on individuals with mild hypercortisolism (excess cortisol) found that low doses of metyrapone were safe. It helped manage blood pressure and showed promise without major safety concerns.
Hydrocortisone, another treatment in this study, often replaces cortisol in the body when natural levels are low. This is common in various medical treatments and is generally considered safe when administered in controlled doses.
In this Phase 4 trial, both treatments have been studied before, providing an understanding of their safety in humans. However, like any treatment, side effects may occur, so the study team will monitor participants closely. Participants should always communicate any concerns to the study staff.12345Why are researchers enthusiastic about this study treatment?
Researchers are excited about these treatments because they explore how manipulating cortisol rhythms could impact insulin resistance linked to sleep loss. Unlike traditional treatments that focus on lifestyle changes or medications directly targeting insulin levels, these treatments use Metyrapone to block cortisol production and hydrocortisone to replace it in a controlled manner. The unique feature here is the precision in timing and dose adjustments to mimic natural cortisol rhythms, which could offer new insights into managing insulin resistance, particularly for those with disrupted sleep patterns.
What evidence suggests that this trial's treatments could be effective for insulin resistance?
Research has shown that metyrapone, a medication used to control cortisol levels, can aid in blood sugar management. In some studies, individuals with type 2 diabetes improved their blood sugar control. For instance, two participants experienced a reduction in their HbA1c levels (a measure of average blood sugar) by at least 0.5%. Metyrapone has also been associated with lower blood pressure in other conditions. This trial will investigate the effects of metyrapone and hydrocortisone on insulin resistance under varying cortisol rhythm conditions, suggesting potential benefits for insulin resistance and related health issues.15678
Who Is on the Research Team?
Peter Liu, MBBS, PhD
Principal Investigator
Lundquist Institute of Biomedical Innovation at Harbor-UCLA Medical Center
Hans P.A. Van Dongen, PhD
Principal Investigator
Washington State University
Are You a Good Fit for This Trial?
This trial is for healthy men and women aged 18-45 with a BMI between 18-25, stable weight, no current medications (including hormones), no major medical or psychiatric issues, not pregnant, non-smokers, and no history of drug/alcohol abuse. Women must have regular menstrual cycles.Inclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants undergo sleep restriction and circadian misalignment with cortisol rhythm manipulation using a dual-hormone clamp
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Metyrapone And Hydrocortisone
Trial Overview
Researchers are studying how changes in the timing of cortisol (a stress hormone) affect insulin resistance during sleep restriction. Participants will receive insulin, dextrose (sugar), metyrapone, and hydrocortisone under controlled lab conditions to mimic different hormone rhythms.
How Is the Trial Designed?
4
Treatment groups
Active Control
Placebo Group
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.
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.
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.
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.
Find a Clinic Near You
Who Is Running the Clinical Trial?
Washington State University
Lead Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Collaborator
Citations
NCT07494084 | Sleep Loss and Circadian Misalignment
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 ...
Efficacy and Tolerability of Metyrapone in Mild Autonomous ...
Evening metyrapone was associated with significant reductions in systolic and diastolic blood pressure in patients with MACS, without causing adrenal ...
Efficacy and Tolerability of Metyrapone in Mild Autonomous ...
Evening metyrapone was associated with significant reductions in systolic and diastolic blood pressure in patients with MACS, without causing ...
Effects of metyrapone in patients with mild hypercortisolism
Glucometabolic control improved in 4 patients, notably in those with type 2 diabetes, with a reduction in HbA1c ≥ 0.5% in two patients without changes in ...
Delta Sleep Response to Metyrapone in Post-Traumatic ...
Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in ...
Sleep Loss for Insulin Resistance · Info for Participants
The purpose of this study is to examine the impact of timed cortisol release or differently timed cortisol rhythms on insulin resistance in ...
SUN-448 Overnight Metyrapone Therapy in Patients with Mild ...
Objectives: To evaluate the tolerability and safety of overnight metyrapone in adults with MACS. ... Association of Insulin Resistance and ...
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