Inhaled Oxytocin and HPA Axis Reactivity

NCT03593473 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 12-2061R01HD093901-01A1
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

Mothers who were enrolled in the Mood, Mother and Infant study will be eligible to participate in the 6-year follow-up maternal visit. At the time of this visit, mothers will be randomized to a single 24 IU dose of nasal oxytocin or placebo. Following administration of the study drug, women will participate in the Trier Social Stress Test (TSST), and blood samples will be collected to quantify HPA axis reactivity.

Conditions

Depression, Postpartum; Anxiety Disorders; Stress, Psychological

Keywords

Oxytocin; Hypothalamic-pituitary-adrenal axis (HPA)

Outcome Measures

Primary Outcomes (1)

• Mean Cortisol (CRT) During Trier Social Stress Test (TSST)

  The study drug will be administered 40 minutes before the TSST. Serum cortisol will be measured via peripheral IV 40 (-40) and 20 (-20) minutes before the TSST, at the start of the TSST (0 minutes), and at minutes 10 (during the speech task), 15 (during the math task), 28, 38, and 48 (during recovery).

  -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes

Secondary Outcomes (4)

• Mean Adrenocorticotropic Hormone (ACTH ) During TSST

  -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes

• Lagged Association Between ACTH and CRT During the TSST

  ACTH at -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes and Cortisol at -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes

• Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST

  Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48

• Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST

  Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48

Other Outcomes (8)

• Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Cortisol (CRT) During Trier Social Stress Test (TSST)

  -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes

• Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Adrenocorticotropic Hormone (ACTH ) During TSST

  -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes

• Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in High Frequency Heart Rate Variability, an Index of Parasympathetic Activity, During the TSST

  Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 0 to 5, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48

Study Arms (2)

Intranasal Oxytocin

EXPERIMENTAL

Participants block randomized to Oxytocin intranasal spray by risk status at enrollment in the Mood, Mother and Infant (MMI) study and as verified by structured clinical diagnostic interview (no history of depression or anxiety, past depression or anxiety, current depression or anxiety).

Drug: Intranasal Oxytocin

Placebo

PLACEBO COMPARATOR

Participants block randomized to placebo Intranasal spray with all equivalent ingredients except oxytocin. Blocks will be stratified by risk status at enrollment in the Mood, Mother and Infant (MMI) study and as verified by structured clinical diagnostic interview (no history of depression or anxiety, past depression or anxiety, current depression or anxiety).

Drug: Placebo

Interventions

Intranasal Oxytocin DRUG

Six intranasal sprays of oxytocin. Each insufflation delivers 4 IUs of oxytocin for a total oxytocin dosage of 24 IUs.

Also known as: Syntocinon

Intranasal Oxytocin

Placebo DRUG

Six intranasal sprays of placebo manufactured to mimic oxytocin nasal spray containing all equivalent ingredients except oxytocin.

Also known as: Inactive

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Singleton pregnancy;
• Intention to breastfeed (due to the centrality of breastfeeding to the oxytocin assessment);
• Intention to remain within 40 miles of the University of North Carolina - Chapel Hill through infant's first birthday;
• Ability to communicate in English.
• Maternal diagnosis of Axis I disorders other than unipolar depression or anxiety disorders. Women with a history of bipolar disorder were excluded, given their increased risk of postpartum psychosis.
• Active substance abuse at enrollment in the 3rd trimester of pregnancy (Tobacco, alcohol, illicit substances);
• Major congenital anomaly;
• Chronic medication/medical condition contraindicated for breastfeeding;
• Current use of tricyclic antidepressants, which alter cortisol and heart rate variability.
• At enrollment, all participants underwent a Structured Clinical Interview Non-Patient version (SCID-NP).

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of North Carolina School of Medicine

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Mills-Koonce WR, Grewen K, O'Shea NG, Pearson B, Strange CG, Meltzer-Brody SE, Guintivano JD, Stuebe AM. The Mood, Mother and Child Study: Protocol for a Prospective Longitudinal Study and Randomized Controlled Trial. JMIR Res Protoc. 2023 Oct 26;12:e51132. doi: 10.2196/51132.

  PMID: 37883133 DERIVED

Related Links

• Mood, mother and infant study web site

MeSH Terms

Conditions

Depression, Postpartum; Anxiety Disorders; Stress, Psychological

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Alison Stuebe, MD, MSc
• Organization: University of North Carollina at Chapel Hill

astuebe@med.unc.edu

919-966-1601

Study Officials

• Alison M Stuebe, MD, MSc

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will receive a nasal insufflation bottle of oxytocin intranasal spray or placebo intranasal spray manufactured to mimic oxytocin nasal spray.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Non-pregnant women will be randomized to either 24 IU of nasal OT or placebo. The Investigational Drug Service will use a random number generator to prepare a randomization table.

Study Record Dates

• First Submitted: June 5, 2018
• First Posted: July 20, 2018
• Study Start: February 7, 2019
• Primary Completion: July 25, 2023
• Study Completion: July 25, 2023
• Last Updated: August 8, 2025
• Results First Posted: May 24, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB) and executes a data use/sharing agreement with the University of North Carolina (UNC).
• Access Criteria: Individual level data sharing will be subject to local IRB approval, individual written informed consents, and national law

Locations

US (1)