Clinical trial NCT06143059: The Effects of Sex Hormones and Alcohol on Sleep
Official title: Sex and Sex Hormone Factors Influencing Acute Alcohol Effects on Sleep Physiology
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Alcohol Use Disorder
Keywords: Sex hormones
Sleep disruption
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: Ohio State University
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2023-11-22
Enrollment: 130
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Women will complete one alcohol-placebo session pair during the mid-follicular phase of the menstrual cycle and one pair during the late luteal phase. Men will complete two session pairs at matched intervals.
Primary purpose: BASIC_SCIENCE

Brief summary: Rates of heavy drinking and Alcohol Use Disorder (AUD) are increasing in women, but research on alcohol-related harms in women - including alcohol's impact on sleep - has been minimal. Numerous studies in men show that alcohol impairs sleep, and preliminary evidence suggests that women may be even more sensitive to alcohol-disrupted sleep due to their sex hormones, which fluctuate across both their menstrual cycles and their reproductive lifespans.

This study will investigate the influence of sex, menstrual cycle phase, and sex hormones on alcohol-disrupted sleep in adults ages 21-45. Healthy women and men will complete two sets of placebo-controlled lab sessions, during the mid-follicular and late luteal phases of female participants' menstrual cycles. During these sessions, participants will receive a dose of alcohol or a placebo (saline) and they will then be monitored (with polysomnography) while they sleep. At-home sleep and alcohol use will also be measured through actigraphy, daily sleep and wake diaries, and alcohol wrist sensors.

Investigators hypothesize that women will show greater disruption of sleep following alcohol use or administration than men, and that alcohol-disrupted sleep will be more pronounced in the late luteal phase compared to the mid-follicular phase. Investigators also expect that estradiol will be negatively associated with alcohol-disrupted sleep, whereas progesterone will be positively associated with alcohol-disrupted sleep.

Detailed description: Rates of heavy drinking and Alcohol Use Disorder (AUD) are increasing in women at an alarming pace. Such drastic increases in drinking will have a significant negative impact on women's health. Unfortunately, until recently heavy drinking has been considered a male-oriented problem, and consequently research on alcohol-related harms in women has been minimal. One specific aspect of women's health that may be negatively affected by alcohol is sleep. Numerous studies in men show that although alcohol has an initial sedative effect, it leads to frequent awakenings and impaired rapid eye movement sleep in the second half of the night.

Preliminary evidence suggests that women experience similar impairment, and that they may be even more sensitive to alcohol-disrupted sleep than men. Further, in the general population, women are at greater risk for insomnia and sleep disturbances than men, in part because women's sleep is sensitive to fluctuations in ovarian hormones. Hormonal influences on sleep are especially pronounced in older women of late reproductive age. However, the influence of sex and sex hormones on alcohol-disrupted sleep across the reproductive lifespan in women is unknown.

Here, investigators will determine the influence of sex, menstrual cycle phase, and sex hormones on alcohol-disrupted sleep in adults across the reproductive age range for women. Healthy women and men (age 21-45) will complete two pairs of experimental sessions in which they receive a dose of alcohol (target breath alcohol content \[BrAC\] = 100mg%, intravenous) or placebo (saline) one hour prior to eight hours of polysomnographically-monitored sleep in the lab. Women will complete one alcohol-placebo session pair during the mid-follicular phase of the menstrual cycle and one pair during the late luteal phase. Men will complete two session pairs at matched intervals. Participants will also complete two 5-day at-home monitoring periods of naturalistic sleep and alcohol consumption patterns during the mid-follicular and late luteal phases. Sleep and alcohol use will be assessed with actigraphy, daily sleep and wake diaries, and alcohol wrist sensors.

Investigators hypothesize that women will show greater disruption of sleep following alcohol than men and that alcohol-disrupted sleep, measured in lab with polysomnography and at-home with actigraphy, will be more pronounced in the late luteal phase compared to the mid-follicular phase. Investigators also expect that estradiol will be negatively associated with alcohol-disrupted sleep, whereas progesterone will be positively associated with alcohol-disrupted sleep.

This study will provide essential information regarding alcohol effects on sleep across the reproductive age span in women, and critically, how these effects are moderated by sex, menstrual cycle, and fluctuations in sex hormones. Findings will directly inform future interventions aimed at reducing alcohol consumption and the negative impacts of alcohol on sleep in women. Given the wide-ranging impact of sleep on other areas of function, including cognition, stress, and well-being, such interventions will have a substantial positive impact on women's health.

Eligibility criteria: Inclusion Criteria:

* 21-45 years old
* At least a high school education
* Fluency in English
* Report drinking at least twice per week and at least weekly binge episodes (4/5+ drinks for women/men in a 2-hour period)
* Regular ovulatory menstrual cycles (21-35 days in length) for women

Exclusion Criteria:

* Any serious medical problems (e.g., liver disease, cardiac abnormality/arrhythmia, pancreatitis, diabetes, neurological problems, gastrointestinal disorders, hypertension, and congestive heart failure)
* Any clinical sleep disorder, including insomnia and obstructive sleep apnea (OSA)
* Any psychiatric condition that could affect sleep/wake cycles (including major depression, generalized anxiety disorder, bipolar disorder, and post-traumatic stress disorder)
* Any medication use that is likely to affect sleep/wake function or cardiovascular functioning (including antidepressants, anxiolytic or soporific medication, and beta-blockers)
* Taking medication for which alcohol consumption is contraindicated
* Substance use disorder other than mild or moderate alcohol use disorder
* Positive urine screen for illegal drugs other than cannabis
* Currently seeking or past-12-month history of inpatient or intensive treatment for addictive behaviors
* Pregnancy, nursing or planning to become pregnant in the next 3 months for women
* Use of hormonal contraception or planning to begin use of hormonal contraception in the next 3 months for women
* Reports smoking \> 5 cigarettes per day (to avoid acute nicotine effects or withdrawal during experimental sessions)
* Has flushing response to alcohol
* Works the night shift

Primary outcomes:
measure: Slow Wave Sleep Minutes
timeFrame: Night 1 (alcohol administration, late luteal phase; 8 hours)
measure: Slow Wave Sleep Minutes
timeFrame: Night 2 (placebo, late luteal phase; 8 hours)
measure: Slow Wave Sleep Minutes
timeFrame: Night 3 (alcohol administration, mid-follicular phase; 8 hours)
measure: Slow Wave Sleep Minutes
timeFrame: Night 4 (placebo, mid-follicular phase; 8 hours)
measure: Rapid Eye Movement Sleep Minutes
timeFrame: Night 1 (alcohol administration, late luteal phase; 8 hours)
measure: Rapid Eye Movement Sleep Minutes
timeFrame: Night 2 (placebo, late luteal phase; 8 hours)
measure: Rapid Eye Movement Sleep Minutes
timeFrame: Night 3 (alcohol administration, mid-follicular phase; 8 hours)
measure: Rapid Eye Movement Sleep Minutes
timeFrame: Night 4 (placebo, mid-follicular phase; 8 hours)
measure: Wake After Sleep Onset
timeFrame: Night 1 (alcohol administration, late luteal phase; 8 hours)
measure: Wake After Sleep Onset
timeFrame: Night 2 (placebo, late luteal phase; 8 hours)
measure: Wake After Sleep Onset
timeFrame: Night 3 (alcohol administration, mid-follicular phase; 8 hours)
measure: Wake After Sleep Onset
timeFrame: Night 4 (placebo, mid-follicular phase; 8 hours)
measure: Sleep Efficiency
timeFrame: Night 1 (alcohol administration, late luteal phase; 8 hours)
measure: Sleep Efficiency
timeFrame: Night 2 (placebo, late luteal phase; 8 hours)
measure: Sleep Efficiency
timeFrame: Night 3 (alcohol administration, mid-follicular phase; 8 hours)
measure: Sleep Efficiency
timeFrame: Night 4 (placebo, mid-follicular phase; 8 hours)
Secondary outcomes:
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
References: