Plasma Oxytocin in Response to Oral Estradiol Valerate and Ethinylestradiol in Healthy Controls and Patients With AVP-Deficiency
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Relative Change in Plasma Oxytocin
研究概览
简要总结
The PHOENIX study aims to investigate whether oral estradiol valerate (EV) and ethinylestradiol (EE) can stimulate oxytocin (OXT) and neurophysin-1 (NP-1) release in humans. The goal is to assess their potential as a safe diagnostic stimulation test for oxytocin deficiency, particularly in patients with arginine vasopressin (AVP) deficiency.
详细描述
Oxytocin (OXT) and arginine vasopressin (AVP) are hypothalamic peptides involved in water balance and emotional regulation. Patients with AVP-Deficiency (central diabetes insipidus) often experience psychological symptoms such as anxiety and depressed mood, possibly due to coexisting OXT deficiency. Previous research showed that 3,4-Methylenedioxy-N-methylamphetamine (MDMA) can increase plasma OXT in healthy individuals but not in AVP-deficient patients, suggesting a clinically relevant OXT deficiency. However, the side effects of MDMA limit its clinical use as a diagnostic tool. Estrogen is known to stimulate OXT release via estrogen receptor β in the hypothalamus. This study evaluates whether oral estradiol valerate (EV) and ethinylestradiol (EE) can safely and effectively provoke OXT and NP-1 release, offering a potential alternative to MDMA-based tests.
The study consists of two parts:
Part 1 (Proof of Concept): A randomized, double-blind, cross-over trial in healthy adults to compare the stimulatory effects of EV and EE on plasma OXT and NP-1.
Part 2 (Pilot Study): An open-label trial in patients with AVP-Deficiency using the estrogen compound identified as most effective in Part 1, to determine whether OXT and NP-1 responses are blunted compared to healthy controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult healthy controls
- •No medication (including hormonal contraception)
- •Female patients (except post-menopausal): regular cycle (21-35 days of duration) in the last 6 months
- •Confirmed diagnosis of AVP-Deficiency
- •Age ≥ 18 years
- •Female patients (except post-menopausal): regular cycle (21-35 days of duration) in the last 6 months or in the case of hormone replacement therapy, with a 1-week pause from the respective treatment
排除标准
- •Participation in a trial with investigational drugs within 30 days
- •Illicit substance use (except for cannabis) during the last 30 days
- •Consumption of alcoholic beverages >15 drinks/week
- •Tobacco smoking >10 cigarettes/day
- •Pregnancy and breastfeeding
- •Hormonal contraception
- •Migraine with and without aura
- •Any cardiometabolic, cardiovascular, and hematological diseases (including deep vein thrombosis/pulmonary embolism and thrombophilia (DVT/PE))
- •Active liver dysfunction or alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) levels 2.5 times above the normal range
- •Diagnosed chronic kidney disease (CKD) > grade III (GRF < 30ml/min)
- •Participation in a trial with investigational drugs within 30 days
- •Illicit substance use (except for cannabis) during the last 30 days
- •Consumption of alcoholic beverages >15 drinks/week
- •Tobacco smoking >10 cigarettes/day
- •Pregnancy and breastfeeding
- •Hormonal contraception
- •Migraine with and without aura
- •Any cardiometabolic, cardiovascular, and hematological diseases (including DVT/PE and Thrombophilia)
- •Active liver dysfunction or alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) levels 2.5 times above the normal range
- •Diagnosed CKD > grade III (GRF < 30ml/min)
研究组 & 干预措施
Study Part I
Healthy Participants will be randomized to receive either first oral Estradiol Valerate or oral Ethinylestradiol. After a washout-phase of at least 7 days or one menstrual cycle for female participants, the second visit of the study will be conducted. Healthy participants will be blinded to the order.
干预措施: esthinylestradiol (Drug)
Study Part II
Participants will receive only one estrogen formulation. Patients with AVP-Deficiency will be aware of the intervention.
干预措施: esthinylestradiol (Drug)
Study Part II
Participants will receive only one estrogen formulation. Patients with AVP-Deficiency will be aware of the intervention.
干预措施: estradiol valerate (Drug)
Study Part I
Healthy Participants will be randomized to receive either first oral Estradiol Valerate or oral Ethinylestradiol. After a washout-phase of at least 7 days or one menstrual cycle for female participants, the second visit of the study will be conducted. Healthy participants will be blinded to the order.
干预措施: estradiol valerate (Drug)
结局指标
主要结局
Relative Change in Plasma Oxytocin
时间窗: From baseline (0 min) to 300 minutes post-dose.
The primary endpoint is the relative change in plasma oxytocin (OXT) concentrations (pg/mL respectively pM) from baseline to the maximum observed value within 300 minutes after administration of oral estradiol valerate (EV) or ethinylestradiol (EE). Baseline is defined as 100% of the initial pre-dose concentration.
Relative Change in Neurophysin-1
时间窗: From baseline (0 min) to 300 minutes post-dose.
The primary endpoint is the relative change in neurophysin-1 (NP-1) concentrations (pg/mL respectively pM) from baseline to the maximum observed value within 300 minutes after administration of oral estradiol valerate (EV) or ethinylestradiol (EE). Baseline is defined as 100% of the initial pre-dose concentration.
次要结局
- Area Under the Curve (AUC) for Plasma OXT and NP-1(From baseline (0 min) to 300 minutes post-dose.)
- Peak change in plasma OXT/NP-1 levels(From baseline (0 min) to 300 minutes post-dose.)
- Time course of plasma OXT/NP-1 levels(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: time course (von Willebrand factor)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: time course (Protein S)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: time course (D-dimer)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: time course (Factor VIII)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: time course (Fibrinogen)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: peak (von Willebrand factor)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: peak (Protein S)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: peak (D-dimer)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: peak (Factor VIII)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Coagulation Parameters: peak (Fibrinogen)(From baseline (0 min) to 300 minutes post-dose.)
- Changes in Other Endocrine Hormones(From baseline (0 min) to 300 minutes post-dose.)
- List of complaints (LC)(300 minutes post-dose.)
- Subjective Emotional Effects(At baseline (0 min), 30, 60, 90, 120, 150, 180, 210, 240, 270 and 300 minutes and 24 hours post-dose.)
- Adverse effects(300 minutes post-dose.)
- Changes in anxiety assessed by State-Trait Anxiety Inventory (STAI-State and Trait).(Baseline, 90 and 270 minutes post-dose.)
- Emotion Recognition Performance - EmBody/EmFace Task(Baseline and 270 minutes post-dose.)
- Emotion Recognition Performance - Face Recognition Task (FERT)(At 270 minutes post-dose.)
- Vital parameters: blood pressure(30 minutes pre-dose; 0, 30, 60, 120, 150, 180, 210, 240, 270, 300minutes, 24hours post-dose.)
- Vital parameters: heart rate(30 minutes pre-dose; 0, 30, 60, 120, 150, 180, 210, 240, 270, 300minutes, 24hours post-dose.)
- Vital parameters: body temperature(30 minutes pre-dose; 0, 30, 60, 120, 150, 180, 210, 240, 270, 300minutes, 24hours post-dose.)
- Concentration of Plasma Sodium(At 0, 180 and 300 minutes post-dose.)
- Concentration of Plasma Potassium(At 0, 180 and 300 minutes post-dose.)
- Concentration of Saliva Oxytocin(At 0, 60, 90, 120, 180, 270, 300 minutes and 24 hours post-dose.)