Cyclic vs. Constant Estradiol: Regimens' Effects on Brain Health (CEREBRA Study)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in Dorsolateral Prefrontal Cortex (dlPFC) activation during working memory task in women receiving either cyclic or continuous estradiol administration.
研究概览
简要总结
The purpose of this study is to learn more about how estradiol patch treatment affects brain processes, health, and wellbeing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 38 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Ability to give written informed consent.
- •Fluent in written and verbal English, though may use Spanish to speak with study staff if preferred. This criterion is based on methodological necessity and feasibility, to ensure participants can accurately understand task instructions and questionnaire items which are available only in English for this pilot study.
- •Participants must be up to date on age-appropriate cancer screening. Specifically, participants must have had a pap smear within the previous 3 years and a mammogram within the previous 2 years (American College of Obstetricians and Gynecologists, 2026; Health Resources and Services Administration, n.d.). Documentation may be requested to verify screening history.
- •Have estradiol level below 40 pg/ml and follicle stimulating hormone (FSH) level above 25 at Van Visit Day
- •Individuals with high estradiol or low FSH levels may be retested, and eligibility determination will be at the discretion of the Principal Investigator (PI).
- •Report final menstrual period (FMP) occurred between 12 months and 48 months at the time of screening.
- •Right-handed.
- •Participants are required to have at least some college education. Setting a minimum education level reduces variability due to educational disparities and supports the validity and interpretability of cognitive performance data. These tasks involve higher-order verbal learning, memory, and executive processes that can be strongly influenced by educational attainment. The investigators will re-evaluate this criterion in future larger-scale studies as resources allow.
排除标准
- •Current psychiatric diagnosis as assessed by the Mini International Neuropsychiatric Interview (MINI, Sheehan et al., 1998).
- •Active psychiatric illness within the previous 12 months or lifetime diagnosis of a psychotic disorder.
- •Current use of antipsychotic medications or mood stabilizers. Participants may have sporadic use of benzodiazepines during the course of the study as long as they can forgo use at least 4 days prior to study procedures.
- •Current or history of substance use disorder within previous 12 months. However, individuals with mild disorders, disorders solely limited to cannabis or alcohol, and/or those who have achieved close to one year of remission may be eligible at the discretion of the PI.
- •Chronic use of steroid medication and other medications that could impact immune function and alter glucocorticoid levels.
- •Inability to forgo use of non-steroidal anti-inflammatory medications for 4 days prior to the Baseline Visit, Van Visits, and Follow Up Visit.
- •Any current or recent medical, psychiatric or social condition which, in the investigator's opinion, is likely to interfere with the conduct of the study, confound the interpretation of study results, or endanger the subject's well-being.
- •Use of systemic hormone therapy (including but not limited to estradiol, progesterone, testosterone, combined hormonal contraceptives, and other systemic hormonal preparations) within 3 months prior to study enrollment. Use of local vaginal estrogen therapy (e.g., vaginal cream or Estring) is permitted. For participants with a history of systemic hormone use, the study investigator may review treatment history to determine whether postmenopausal status can be confirmed.
- •History of suicidal behavior within the past 2 years
- •Undiagnosed abnormal genital bleeding.
- •Known, suspected, or history of breast cancer.
- •Active deep vein thrombosis, pulmonary embolism, or history of these conditions.
- •History of cardiovascular disease
- •Known liver dysfunction or disease.
- •Needle phobia or history of vasovagal response to phlebotomy.
- •History of clinically relevant claustrophobia or inability to tolerate a scanning environment in the past.
- •Metal in body unsafe for magnetic resonance imaging (MRI) or other conditions that would make MRI unsafe for participants (i.e., aneurysm clip, cardiac pacemaker, etc.).
- •Current treatment with Central nervous system (CNS) depressants (e.g., opioids, benzodiazepines).
- •Treatment with corticosteroids within the past 30 days.
- •Known allergy to progesterone or peanut allergy.
- •Any history of chemotherapy as negative effects on cognitive performance have been reported for years post cessation of treatment (Guida et al., 2021; Koppelmans et al., 2012).
研究组 & 干预措施
Cyclic Estradiol
Transdermal estradiol 100 mcg/day patch applied for 5 days every 21 days for approximately 12 weeks.
干预措施: Cyclic Estradiol (Drug)
Continuous Estradiol
Transdermal estradiol 100 mcg/day patch worn continuously and replaced every 6 days for approximately 12 weeks.
干预措施: Continuous Estradiol (Drug)
结局指标
主要结局
Change in Dorsolateral Prefrontal Cortex (dlPFC) activation during working memory task in women receiving either cyclic or continuous estradiol administration.
时间窗: Baseline and approximately 12 weeks after initiation of study treatment
Description: Dorsolateral prefrontal cortex (dlPFC) activation will be measured during performance of the letter N-back task using functional magnetic resonance imaging (fMRI). Change scores will be calculated from baseline to follow-up.
Change from baseline in extracellular vesicle concentration.
时间窗: Baseline, Days 1-4, Days 21-24, and approximately 12 weeks after treatment initiation
Extracellular vesicle (EV) concentration will be measured from plasma samples and reported as particles per milliliter (particles/mL). Changes from baseline will be assessed following cyclic or continuous estradiol administration.
Change from baseline in extracellular vesicle size.
时间窗: Baseline, Days 1-4, Days 21-24, and approximately 12 weeks after treatment initiation
Extracellular vesicle (EV) size will be measured from plasma samples and reported in nanometers (nm). Changes from baseline will be assessed following cyclic or continuous estradiol administration.
Change from baseline in extracellular vesicle zeta potential.
时间窗: Baseline, Days 1-4, Days 21-24, and approximately 12 weeks after treatment initiation
Extracellular vesicle (EV) zeta potential will be measured from plasma samples and reported in millivolts (mV). Changes from baseline will be assessed following cyclic or continuous estradiol administration.
Change in C-reactive protein concentration.
时间窗: Baseline and approximately 12 weeks after initiation of study treatment
Serum C-reactive protein concentration measured using the Meso Scale Discovery (MSD) V-PLEX Neuroinflammation Panel.
Change in interleukin concentration.
时间窗: Baseline and approximately 12 weeks after initiation of study treatment
Interleukin concentration measured using the MSD V-Plex Neuroinflammation Panel.
Change in cytokine concentration.
时间窗: Baseline and approximately 12 weeks after initiation of study treatment
Cytokine concentration measured using the MSD V-Plex Neuroinflammation Panel.
Change in chemokine concentration.
时间窗: Baseline and approximately 12 weeks after initiation of study treatment
Chemokine concentration measured using the MSD V-Plex Neuroinflammation Panel.
Change in growth factor concentration.
时间窗: Baseline and approximately 12 weeks after initiation of study treatment
Growth factor concentration measured using the MSD V-Plex Neuroinflammation Panel.
次要结局
- Change in executive function symptoms on the Brown Attention-Deficit Disorder Scale (BADDS).(Baseline and approximately 12 weeks after initiation of study treatment)
- Change in perceived stress on the Perceived Stress Scale (PSS).(Baseline and approximately 12 weeks after initiation of study treatment)
- Change in depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).(Baseline and approximately 12 weeks after initiation of study treatment)
- Change in anxiety symptoms on the Generalized Anxiety Disorder-7 (GAD-7).(Baseline and approximately 12 weeks after initiation of study treatment)
- Change in hair cortisol concentration.(Baseline and approximately 12 weeks after initiation of study treatment)