An interventional study of estradiol valerate and esthinylestradiol in AVP Deficiency and Diabetes Insipidus, sponsored by University Hospital, Basel, Switzerland. Recruiting at 1 site in Switzerland. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-11.
Sponsored by University Hospital, Basel, Switzerland · Not applicable, Interventional, and Diagnostic
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.
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.
27 studies on the registry are indexed under Diabetes Insipidus, Neurogenic; 12 are open to participants now.
This study's planned enrollment of 28 is below the median of 42 across 23 interventional studies indexed under Diabetes Insipidus, Neurogenic.
Browse Diabetes Insipidus, Neurogenic studies →University Hospital, Basel, Switzerland is the lead sponsor of 990 studies on the registry; 189 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Part 1
Part 2
Exclusion Criteria:
Part 1
Part 2
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: estradiol valerate · Drug: esthinylestradiol
Participants will receive only one estrogen formulation. Patients with AVP-Deficiency will be aware of the intervention.
Drug: estradiol valerate · Drug: esthinylestradiol
estradiol valerate
estradiol valerate
Relative Change in Plasma Oxytocin
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.
Time frame: From baseline (0 min) to 300 minutes post-dose.
Relative Change in Neurophysin-1
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.
Time frame: From baseline (0 min) to 300 minutes post-dose.
Area Under the Curve (AUC) for Plasma OXT and NP-1
Time frame: From baseline (0 min) to 300 minutes post-dose.
Peak change in plasma OXT/NP-1 levels
Time frame: From baseline (0 min) to 300 minutes post-dose.
Time course of plasma OXT/NP-1 levels
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: time course (von Willebrand factor)
Time course and peak of coagulation marker von Willebrand factor
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: time course (Protein S)
Time course and peak of coagulation marker Protein S
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: time course (D-dimer)
Time course and peak of coagulation marker D-dimer
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: time course (Factor VIII)
Time course and peak of coagulation marker Factor VIII
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: time course (Fibrinogen)
Time course and peak of coagulation marker Fibrinogen
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: peak (von Willebrand factor)
Peak of coagulation marker von Willebrand factor
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: peak (Protein S)
Peak of coagulation marker Protein S
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: peak (D-dimer)
Peak of coagulation marker D-dimer
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: peak (Factor VIII)
Peak of coagulation marker Factor VIII
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Coagulation Parameters: peak (Fibrinogen)
Peak of coagulation marker Fibrinogen
Time frame: From baseline (0 min) to 300 minutes post-dose.
Changes in Other Endocrine Hormones
Time course of plasma estrogen, testosterone, copeptin, cortisol,Luteinizing Hormone/Follicle-Stimulating Hormone (LH/FSH), and other pituitary hormones.
Time frame: From baseline (0 min) to 300 minutes post-dose.
Subjective Emotional Effects
Changes in subjective feelings assessed by Numeric Rating Scale (NRS). NRS will be repeatedly used to assess subjective alterations in consciousness over time. NRS will be presented as a range from 0 to 10 marked with "not at all" on the left and "extremely" on the right. The following NRS will be used: "any effect", "good effect", "bad effect", "liking", "high", "happy", "fear", "stimulated", "feeling close to others", "concentration", "thinking", "open", and "trust".
Time frame: At baseline (0 min), 30, 60, 90, 120, 150, 180, 210, 240, 270 and 300 minutes and 24 hours post-dose.
Adverse effects
Participants will be asked to report any adverse events that occur during the sessions or between sessions at the start of the next session. The test requires about 2 minutes.
Time frame: 300 minutes post-dose.
List of complaints (LC)
The LC consists of 66 items, yielding a global score measuring physical and general discomfort. The LC list is administered at the beginning and the end of the session with reference to complaints throughout the entire session.
Time frame: 300 minutes post-dose.
Changes in anxiety assessed by State-Trait Anxiety Inventory (STAI-State and Trait).
This is a questionnaire given to adults to determine the general anxiety levels. Based on responses to 20 items, with scores ranging from 1 ("almost never") to 4 ("almost always"), a total score is calculated. The total trait score (STAI-T) ranges from 20 to 80, with higher scores indicating more pronounced anxiety and scores. The STAI-T evaluates relatively stable aspects of "anxiety proneness," including general states of calmness, confidence, and security. A score above 45/80 indicating clinically significant anxiety symptoms. The state score (STAI-S) evaluates the current state of anxiety, asking how respondents feel "right now," using items that measure subjective feelings of apprehension, tension, nervousness, worry, and activation/arousal of the autonomic nervous system. We will use the STAI-T for the baseline visit and the STAI-S for the treatment visits. The test requires about 5 minutes.
Time frame: Baseline, 90 and 270 minutes post-dose.
Emotion Recognition Performance - EmBody/EmFace Task
The EmBody and EmFace subtasks comprise each of 42 stimuli showing body or facial expressions of angry, happy, or neutral affect (14 clips per emotion, half in front view and half in half-profile side view from the left). Stimuli last 1.5 seconds at 24 frames per second and are geometrically and optically standardized to prevent biases induced by ethnic cues (e.g., hair or skin tone) or clothing. Item order is pseudorandom to prevent sequence effects and was determined using the following constraints: the same emotion is shown no more than twice in a row; the same view per emotion is not shown consecutively (i.e., no angry-front, angry-front). The test is performed twice during each treatment visit.
Time frame: Baseline and 270 minutes post-dose.
Emotion Recognition Performance - Face Recognition Task (FERT)
The FERT is used to assess recognition of basic emotions. The task includes 10 neutral faces and 160 faces that express one of four basic emotions (i.e., happiness, sadness, anger, and fear), with pictures morphed between 0% (neutral) and 100% in 10% steps. Two female and two male pictures are used for each of the four emotions. Stimuli are shown in random order for 500 ms and are then replaced by the rating screen where participants have to indicate the correct emotion. The outcome measure is accuracy (proportion correct). The test data is recorded on a computer and processed into scores for each emotion using an established matlab routine according to standard operating procedures (SOP) (clinical pharmacology, Orca DKF). The test is performed once during each treatment visit, exactly 270min after EV/EE administration.
Time frame: At 270 minutes post-dose.
Vital parameters: blood pressure
Blood pressure (systolic and diastolic) will be measured at several timepoints during the treatment visit
Time frame: 30 minutes pre-dose; 0, 30, 60, 120, 150, 180, 210, 240, 270, 300minutes, 24hours post-dose.
Vital parameters: heart rate
Heart rate will be measured at several timepoints during the treatment visit
Time frame: 30 minutes pre-dose; 0, 30, 60, 120, 150, 180, 210, 240, 270, 300minutes, 24hours post-dose.
Vital parameters: body temperature
body temperature will be measured at several timepoints during the treatment visit
Time frame: 30 minutes pre-dose; 0, 30, 60, 120, 150, 180, 210, 240, 270, 300minutes, 24hours post-dose.
Concentration of Plasma Sodium
Sodium concentration (mmol/l) will be assessed in plasma.
Time frame: At 0, 180 and 300 minutes post-dose.
Concentration of Plasma Potassium
Sodium concentration (mmol/l) will be assessed in plasma.
Time frame: At 0, 180 and 300 minutes post-dose.
Concentration of Saliva Oxytocin
Time frame: At 0, 60, 90, 120, 180, 270, 300 minutes and 24 hours post-dose.
Started Jan 2026 (actual). Primary completion is estimated for Feb 2027, 13 months after the start.
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