Clarifying the Endocrinology of Acute Risk 4 (CLEAR-4): Neurocognitive Mechanisms of Perimenstrual Estrogen Effects on Suicidality
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Early-Luteal-to-Perimenstrual Worsening of Daily Passive Suicidal Ideation (PSI)
研究概览
简要总结
This within-person, crossover, 2-condition, placebo-controlled study compares the impact of two perimenstrual conditions on severity of suicidal symptoms in females with past-month suicidality but minimal risk of imminent suicide attempt. The two conditions are (1) perimenstrual administration of estradiol and (2) natural perimenstrual withdrawal from estradiol during placebo.
详细描述
Previous work from our group demonstrates that perimenstrual worsening of suicidal thoughts in females is caused by normal perimenstrual withdrawal from the ovarian steroid estradiol (E2), since perimenstrual administration of E2+P4 or E2 alone prevented the perimenstrual worsening of suicidal ideation observed under placebo. In the present study, we follow up on that work with an additional mechanistic crossover trial in which E2 will be administered perimenstrually (E2 condition) or not (PBO condition) and neurocognitive mechanisms of suicidal symptom improvement will be probed.
50 (30 completers) female outpatients, with past-month suicidal ideation but minimal imminent risk for attempt, will complete self-reports and clinical interviews measuring the presence and severity of suicidal ideation in each of two conditions (A, B: order randomized across two menstrual cycles): (A) perimenstrual E2 withdrawal/depletion (under placebo), (B) perimenstrual administration of E2. A washout cycle will separate conditions. Analyses will compare the perimenstrual trajectories of symptoms and suicidality across the two conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
double-blind
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Ability to adhere to medication regimen
- •Speaks English
- •Assigned female at birth with intact ovaries
- •Premenopausal
- •Normal menstrual cycles between 24-32 days
- •Under current care of an outpatient mental health provider with visits occurring at least once every 3 months.
- •At least 1 year postpartum.
- •Willing to use a barrier method of birth control during the study.
- •Normal weight (BMI between 18-29)
- •Must report at least some recent suicidal ideation (in the past month) at the time of recruitment.
- •Must be categorized as having acceptably low imminent risk for suicidal crisis/attempt by a licensed clinical psychologist utilizing evidence-based clinical and research guidelines for imminent suicide risk management.
排除标准
- •Must not be pregnant, breastfeeding, or trying to become pregnant.
- •Must not be taking any form of exogenous hormones or hormonal intrauterine device, and must have ended previous use of hormonal preparations at least one month prior to the study.
- •Must not have a personal history of any chronic medical condition, including but not limited to metabolic or autoimmune disease, epilepsy, endometriosis, cancer, diabetes, cardiovascular, gastrointestinal, hepatic, renal, or pulmonary disease, and no personal or first degree family history of thromboembolic events.
- •Any current cigarette smoking is exclusionary.
- •Must not report a history of clinical diagnosis or treatment for postpartum depression or premenstrual dysphoric disorder (Note: Premenstrual Dysphoric - - - Disorder diagnosis must have been made based on prospective daily ratings).
- •Must not report any history of manic episode, any history of psychotic symptoms, or current substance use disorder.
研究组 & 干预措施
Transdermal Estradiol
.1mg per 24 hours transdermal estradiol applied to the skin weekly, for 14 days.
干预措施: Transdermal Estradiol (Drug)
Placebo
Clear patch manufactured to mimic the E2 patch applied to the skin weekly, for 14 days.
干预措施: Placebo (Other)
结局指标
主要结局
Early-Luteal-to-Perimenstrual Worsening of Daily Passive Suicidal Ideation (PSI)
时间窗: Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6
Three daily survey questions assessing PSI will be administered each day (i.e., "I wished I were dead", "I wish I could go to sleep and not wake up", "I thought that life was not worth living"; scale from 1 (Not at All) to 5 (Extremely)). Composite mean scores for these 3 items are computed, providing a single number for each day, with higher daily values representing more severe PSI. Early-luteal-to-perimenstrual worsening of daily PSI is estimated for each person in each condition as the mean of scores in the perimenstrual phase (Days -3 to +1 relative to menses onset) minus the mean in the early luteal phase (Days +2 to +6 relative to the luteinizing hormone surge at day 0).
Early-Luteal-to-Perimenstrual Worsening of Daily Active Suicidal Ideation (ASI)
时间窗: Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6
Three daily survey questions assessing ASI will be administered each day (i.e., "I thought about killing myself", "I wanted to kill myself", "I had the urge to kill myself"; scale from 1 (Not at All) to 5 (Extremely)). Composite mean scores for these 3 items are computed, providing a single number for each day, with higher daily values representing more severe ASI. Early-luteal-to-perimenstrual worsening of daily ASI is estimated for each person in each condition as the mean of scores in the perimenstrual phase (Days -3 to +1 relative to menses onset) minus the mean in the early luteal phase (Days +2 to +6 relative to the luteinizing hormone surge at day 0).
Early-Luteal-to-Perimenstrual Increase in the Probability of Daily Suicidal Planning (SP)
时间窗: Mean daily dichotomous outcome (ranging from 0-1) in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean in the early luteal phase (Days +2,
Two questions from the ASIQ assessing SP will be administered each day in an adapted daily format (i.e., "I thought about how I might kill myself", "I thought about when I might kill myself"; scale from 1 (Not at All) to 5 (Extremely)). Daily dichotomous scores will be derived such that if either of these two items are endorsed with a score higher than 1 (not at all) on a given day, the composite score will be 1 (otherwise the score will be 0) for that day. Early-luteal-to-perimenstrual increase in the probability of daily SP is estimated for each person in each condition as the mean of dichotomous daily scores in the perimenstrual phase (Days -3 to +1 relative to menses onset) minus the mean of dichotomous scores in the early luteal phase (Days +2 to +6 relative to the luteinizing hormone surge at day 0).
次要结局
- Perimenstrual Reward Positivity (RewP)(Mean RewP amplitude in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline))
- Early-Luteal-to-Perimenstrual Worsening of daily self-reported anhedonia(Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6)
- Early-Luteal-to-Perimenstrual change (improvement) in daily N-Back performance(Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6)
- Early-Luteal-to-Perimenstrual Worsening of daily self-reported working memory failures (WMF)(Mean daily rating in the perimenstrual phase (Days -3, -2, -1, and +1 relative to menses onset where menses onset is day +1 and there is no 0 on the menses-onset timeline) minus the mean daily rating in the early luteal phase (Days +2, +3, +4, +5, and +6)
研究者
Tory Anne Eisenlohr-Moul
Associate Professor of Psychiatry
University of Illinois at Chicago