Identifying Oxytocin Deficiency in Pediatric Patients With Pituitary Disease (Pedi-EVOLVE)

Identifying a Provocation Test for Diagnosis of Oxytocin Deficiency in Youth With Hypopituitarism

An open-labeled, interventional pilot trial, 10 youth with AVP-D and 10 PD matched for age, sex, and BMI will be recruited from Pediatric Endocrinology and Neuroendocrinology at Massachusetts General Hospital and in the community. This study tests the hypothesis that oral estrogen/progestin will stimulate endogenous oxytocin release in control subjects. Eligible participants will receive two tablets in a single administration containing a total of 1 mg of norethindrone acetate 70 mcg of ethinyl estradiol. Sampling for blood and saliva will take place at baseline and approximately 24 hours following study drug administration. Neuropsychological assessment (anxiety, mood and emotion regulation; impulse control; aberrant eating behaviors; social cognition and functioning; quality of life) will be assessed at baseline to characterize the study population.

Study Overview

• Status: Recruiting
• Conditions: Hypopituitarism; Oxytocin Deficiency; Pediatric Disease; Arginine Vasopressin Deficiency
• Intervention / Treatment: Drug: Norethindrone Acetate-Ethinyl Estradiol

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Hannah Lamont, PhD; Phone Number: 617-726-1347; Email: MGHHypopit@MGH.HARVARD.EDU

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Hannah Lamont, PhD; Phone Number: 617-726-1347; Email: MGHHypopit@MGH.HARVARD.EDU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria (participants with AVP-D):

• AVP-D diagnosed in clinic using standard of care diagnostic tools;
• Stable pituitary hormone replacement (no change in dose of hormone replacement in six weeks prior to baseline);
• If on estrogen/progestin, female participants agree to stop for at least 6 weeks prior to Main study visits;
• English language proficiency.

Inclusion criteria (participants with hypopituitary disease):

• Hypopituitary disease diagnosis;
• If receiving pituitary hormone replacement, no change in dose in six weeks prior to baseline);
• If on estrogen/progestin, participants agree to stop for at least 6 weeks prior to Main study visits;
• English language proficiency.

Exclusion criteria (all participants):

• History of pulmonary embolism or unprovoked deep venous thrombosis;
• History of breast/endometrial cancer as well as current therapies on estrogen modulators/blockers (i.e., tamoxifen, raloxifene, aromatase inhibitors);
• History of stroke, transient ischemic attack, myocardial infarction, angina pectoris, or peripheral arterial disease;
• Pregnancy or breastfeeding within the last 8 weeks;
• Medication changes within 2 weeks of enrollment or within 5 half-lives of the respective medication;
• History of stage 3 chronic kidney disease or cirrhosis;
• Any significant illness or condition that the investigator determines could interfere with study participation, data collection or safety;
• Active tobacco smoking or nicotine patch use;
• Psychosis or active suicidality.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individuals with hypopituitary disease with Arginine-vasopressin deficiency (AVP-D).; Norethindrone Acetate-Ethinyl Estradiol will be given to participants with arginine-vasopressin deficiency.	Drug: Norethindrone Acetate-Ethinyl Estradiol; Norethindrone Acetate-Ethinyl Estradiol will be given to participants in both cohorts, arginine-vasopressin deficiency cohort and control cohort.; Other Names: Estrogen-progestin
Experimental: Individuals with hypopituitary disease (without AVP-D); Norethindrone Acetate-Ethinyl Estradiol will be given to control subjects.	Drug: Norethindrone Acetate-Ethinyl Estradiol; Norethindrone Acetate-Ethinyl Estradiol will be given to participants in both cohorts, arginine-vasopressin deficiency cohort and control cohort.; Other Names: Estrogen-progestin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in neurophysin-1 from baseline	Change in neurophysin-1 levels from baseline to 24 hours	0 minutes (Baseline) and 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in oxytocin from baseline	Change in oxytocin from baseline to 24 hours	0 minutes (Baseline) and 24 hours

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Elizabeth A Lawson, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Hypothalamic Diseases; Pituitary Diseases; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Hypopituitarism; norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination
• Other Study ID Numbers: 2025P001958

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No