Using Allopregnanolone to Probe Behavioral and Neurobiological Mechanisms That Underlie Depression in Women During the Perimenopause
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Within-person change in score on the Ruminative Responses Scale
研究概览
简要总结
This study aims to identify how the progesterone metabolite allopregnanolone affects behavior and neurobiology that may underlie perimenopausal depression.
详细描述
Midlife women are burdened with depression risk that is at least partly attributed to changing reproductive steroid dynamics across a prolonged reproductive transition. The investigators hypothesize that declining endogenous allopregnanolone (ALLO) levels across the menopause transition underlies perimenopausal depression. This mechanistic trial aims to amplify the contrast between lower endogenous ALLO levels in perimenopausal women and higher levels experimentally induced by exogenous ALLO. This will be achieved by using the exogenous ALLO treatment, brexanolone, which is FDA-approved to treat depression in postpartum patients, in a randomized, double-blind, parallel-arm, placebo-controlled trial. By manipulating ALLO levels together with key measurement of depression domains, this study harnesses the endocrine biology of perimenopause to explicate behavioral and neurobiological mechanisms underlying depression in perimenopausal women.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Healthy perimenopausal women ages 40 to 60 years
- •Depressive symptoms
- •Able to read Arabic numerals and perform simple arithmetic
- •Able to provide written informed consent
排除标准
- •Use of medications to treat depression
- •Systemic hormone therapy
- •Contraindicated medications with brexanolone
- •Other psychiatric illnesses that are considered to be primary
- •Current suicidal ideation
- •Active substance use disorders
- •Unstable medical conditions
- •Obstructive sleep apnea or other primary sleep disorders
- •Abnormal hepatic and renal function
- •Known allergy to progesterone, exogenous allopregnanolone, or brexanolone
- •History of head injury resulting in loss of consciousness > 20 min
- •Inability to comply with barrier contraceptive methods
- •Known intellectual disability
- •Investigator judgement that study participation constitutes substantial risk given medical or psychiatric condition
- •Current or recent participation in clinical trial expected to interfere with risk of or interpretation of study data
- •Inability to comply with study procedures
研究组 & 干预措施
brexanolone
Participants will receive a continuous 60-hr intravenous infusion of brexanolone
干预措施: brexanolone (Drug)
placebo
Participants will receive a continuous 60-hr infusion of placebo
干预措施: placebo (Drug)
结局指标
主要结局
Within-person change in score on the Ruminative Responses Scale
时间窗: Baseline to 4 days
The Ruminative Responses Scale (RRS) comprises 22 items which ask how frequently the participant thinks certain statements when they feel depressed. Each item is scored from 1-4. Total scores range from 22-88 with higher scores indicating more severe rumination.
次要结局
未报告次要终点
研究者
Hadine Joffe, MD MSc
Study Principal Investigator
Brigham and Women's Hospital