Allopregnanolone and Dynamic GABA-A Receptor Plasticity in Selective Serotonin Reuptake Inhibitor Responsive Premenstrual Dysphoric Disorder
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 288
- 试验地点
- 4
- 主要终点
- Neuroactive Steroid Levels
研究概览
简要总结
Premenstrual dysphoric disorder (PMDD) is a severe affective disorder impacting millions of women worldwide, thought to be due to altered sensitivity to hormone fluctuations across the menstrual cycle. Neuroactive steroid hormones (NAS) and the gamma-aminobutyric acid (GABA)-A receptor (GABAAR) are thought to play a role in PMDD. This research will assess the blood levels of GABAergic NAS, expression of associated enzymes, and expression of GABAAR subunits across the premenstrual (luteal) phase of the menstrual cycle in healthy controls and individuals with PMDD. Within the PMDD group, the investigators will assess how these measures are affected by a low-dose antidepressant medication versus placebo. The results will provide a comprehensive view of the changes in these systems across the menstrual cycle and will add to the investigator's understanding of the mechanisms that underlie PMDD, as well as therapeutic mechanisms of PMDD treatment.
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
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •female sex,
- •fluent in the English language
- •regular menstrual cycles (24-35 days)
- •age 18-50 years old
- •ability to give written informed consent
排除标准
- •psychiatric medication use in the past 2 months
- •substance use disorder in the past 6 months
- •lifetime history of psychotic disorder including schizophrenia
- •schizoaffective disorder, major depression with psychotic features
- •history of psychiatric disorder other than PMDD in past year
- •active suicidal ideation with plan or attempt in past 6 months
- •steroid hormone or hormonal contraceptive use (except levonorgestrel as emergency contraceptive) in past 2 months
- •pregnancy in past 6 months
- •history of brain injury
- •current or history of endocrine disorder including uncontrolled diabetes or thyroid disease
- •History of arrythmias, severe liver impairment, history of seizure disorder
- •If currently taking the following meds: methylene blue, linezolid
- •Other prohibited concomitant meds are Monoamine oxidase inhibitors (MAOIs), pimozide, and disulfiram
研究组 & 干预措施
PMDD with sertraline
Participants delegated to the "PMDD with sertraline" arm will be individuals with severe premenstrual symptoms in the luteal phase of the menstrual cycle. Participants will be asked to track mood across two menstrual cycles, answer self-report surveys, and complete eight blood draws (four in each menstrual cycle). In the second cycle, participants in this arm will take a daily pill of 50 mg of sertraline from ovulation until menses onset (end of menstrual cycle 2).
干预措施: sertraline 50 mg daily (Drug)
PMDD with placebo
Participants delegated to the "PMDD with placebo" arm will be individuals with severe premenstrual symptoms in the luteal phase of the menstrual cycle. Participants will be asked to track mood across two menstrual cycles, answer self-report surveys, and complete eight blood draws (four in each menstrual cycle). In the second cycle, participants in this arm will take a daily placebo pill from ovulation until menses onset (end of menstrual cycle 2).
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Neuroactive Steroid Levels
时间窗: Post ovulation up to 2 days, up to 5 days pre-menses prediction
The primary outcome variable is levels of neuroactive steroids in blood; from the early luteal phase (2 days post ovulation) compared to the late luteal phase (days 5 to 1 prior to predicted menses onset)
次要结局
- Neurosteroidogenic enzyme expression levels(First menstrual cycle, up to 3 months)
- GABAAR subunit expression levels(first menstrual cycle, up to 3 months)