Clinical trial NCT04037605: Hormonal Mechanisms of Sleep Restriction - Axis Study in Older Men and Postmenopausal Women
Official title: Hormonal Mechanisms of Sleep Restriction - Axis Study in Older Men and Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Sleep Restriction
Keywords: Testosterone
Cortisol
Lead sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Sponsor class: OTHER
First posted: 2019-07-30
Enrollment: 5
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Blood is sampled every 10 minutes from 4 pm to 9 pm for future mathematical deconvolution in order to determine hormone pulse characteristics in response to the clamp conditions.
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Average Blood Cortisol Concentration
timeFrame: 5 days
measure: Average Blood Testosterone Concentration
timeFrame: 5 days
Secondary outcomes:
measure: Peak Blood Cortisol Concentration
timeFrame: 5 days
measure: Peak Blood Testosterone Concentration
timeFrame: 5 days
measure: Trough Blood Cortisol Concentration
timeFrame: 5 days
measure: Trough Blood Testosterone Concentration
timeFrame: 5 days
measure: Reaction time on Psychomotor Vigilance Task
timeFrame: 5 days
measure: Karolinska Sleepiness Scale
timeFrame: 5 days
measure: Two card gambling task
timeFrame: 5 days
measure: Modified Sternberg working memory test
timeFrame: 5 days
measure: Caloric Intake
timeFrame: 5 days
measure: Hunger
timeFrame: 5 days
measure: Food Cravings
timeFrame: 5 days
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute
state: California
Study officials:
affiliation: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
name: Peter Liu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: