Plasma Oxytocin Response to Oral Estrogens in Healthy Controls and AVP-Deficiency

NCT07361263 | Recruiting

• 1 other identifier: 2025-02197;kt25ChristCrain5
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

AVP Deficiency; Diabetes Insipidus

Keywords

Oxytocin; estradiol valerate; ethinylestradiol

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From baseline (0 min) to 300 minutes post-dose.

Secondary Outcomes (26)

• 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.

Study Arms (2)

estradiol valerate

EXPERIMENTAL

Drug: estradiol valerate

esthinylestradiol

EXPERIMENTAL

Drug: esthinylestradiol

Interventions

estradiol valerate DRUG

estradiol valerate

estradiol valerate

esthinylestradiol DRUG

estradiol valerate

esthinylestradiol

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Part 1
• 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
• Part 2
• 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

You may not qualify if:

• Part 1
• Participation in a trial with investigational drugs within 30 days
• BMI \>30
• Age \>50
• 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)
• Part 2
• Participation in a trial with investigational drugs within 30 days

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

MeSH Terms

Conditions

Diabetes Insipidus, Neurogenic; Diabetes Insipidus

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Mirjam Christ-Crain, Prof. Dr.

  University Hospital of Basel

  STUDY CHAIR

Central Study Contacts

Andi Nikaj, MD

CONTACT

+41 61 328 57 43; andi.nikaj@usb.ch

Ursula Gobrecht-Keller, MD

CONTACT

+41 61 32 86028; ursula.gobrecht@usb.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will be conducted in two parts. Part 1 is a double-blinded, randomized cross-over proof-of-concept trial in healthy adults. Part 2 is an open-labeled single arm pilot study in adults with an established diagnosis of AVP-Deficiency. Study parts 1 and 2 will be conducted consecutively. For part 1 16 participants will be enrolled and for part 2 12 patients will be enrolled.

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 22, 2026
• Study Start: January 9, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

CH (1)