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

Sleep Restriction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04037605
• Other study ID #: P31056-01R
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: February 9, 2020
• Est. completion date: July 24, 2024

Study information

• Verified date: November 2023
• Source: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Sleep restriction and its consequences are major public health problems, especially in older adults. Among the more severe physiological sequelae of sleep restriction is the development of insulin resistance. The mechanisms by which sleep restriction leads to increased insulin resistance are unknown, especially in vulnerable older adults; such research informs development of targeted interventions against the sleep loss/insulin resistance link.

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 40 participants can be enrolled. However, participants will be allowed an opportunity to be randomized to all 4 conditions so that as few as 10 participants may be required. We anticipate 5 men and 5 women will be enrolled assuming each undergoes all 4 clamp conditions.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 5
• Est. completion date: July 24, 2024
• Est. primary completion date: July 24, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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

• Mini- mental state examination (MMSE) < 27

Related Conditions & MeSH terms

• Sleep Restriction

Intervention

Drug:
• Ketoconazole Pill (also known as nizoral)
Ketoconazole pill is taken 4 times per inpatient visit
• Ganirelix
Ganirelix subcutaneous injection is administered twice per inpatient visit
• Dexamethasone Pill
Dexamethasone pills is taken twice per inpatient visit
• Dexamethasone injection
Dexamethasone IV injection is given twice per inpatient visit
• Cosyntropin Injectable Product
Cosyntropin injection is given twice per inpatient visit
• Recombinant Human Luteinizing Hormone (also known as luveris)
Recombinant Human Luteinizing Hormone is given as 6 IV infusion pulses per inpatient visit
• Hydrocortisone Injection (also known as solu-cortef)
Hydrocortisone IV push is given twice per inpatient visit
• Gonadorelin (also known as Lutrepulse)
Gonadorelin IV injection is given twice per inpatient visit
• Corticorelin (also known as Acthrel)
Corticorelin IV injection is given twice per inpatient visit
• Placebo oral tablet
Placebo for Ketoconazole are given 4 times per inpatient visit
• Saline Solution
Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per inpatient visit
• Saline solution for injection
Saline Solution (placebo) for ganirelix subcutaneous injection

Locations

Country	Name	City	State
United States	Los Angeles Biomedical Research Institute	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	5 days
Secondary	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.	5 days
Secondary	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.	5 days
Secondary	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.	5 days
Secondary	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.	5 days
Secondary	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.	5 days
Secondary	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'.	5 days
Secondary	Modified Sternberg working memory test	Computerized neurobehavioral testing to determine how 4 nights of sleep restriction affects reaction time and accuracy.	5 days
Secondary	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.	5 days
Secondary	Hunger	Hunger levels are assessed using the Flint visual analogue scale (VAS) to assess how 4 nights of sleep restriction affects participants' appetite.The Flint VAS asks the participant to rate 8 aspects of their hunger level on a scale from 1-5.	5 days
Secondary	Food Cravings	Food cravings are measured using the Food Cravings Index (FCI) scale to assess which food groups each participant has cravings for and how their cravings change during 4 nights of sleep restriction. The participant ranks their craving for 33 food items on a scale from 1-5.	5 days