Inhaled Oxytocin and HPA Axis Reactivity

NCT ID: NCT03593473

Last Updated: 2025-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-07
• Study Completion Date: 2023-07-25

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.

Detailed Description

The Mood, Mother and Infant Study is a prospective observational cohort study that began enrollment in May of 2013. Women were recruited in the 3rd trimester of pregnancy and followed prospectively through 12 months postpartum. Mother-infant pairs who completed the 12-month visit will be invited to participate in the current Psychobiology of Resilience in Maternal-Child Pairs follow-up study. The trial described here is a randomized controlled trial embedded within the Psychobiology of Resilience study.

Non-pregnant women will be randomized to either 24 IU of nasal oxytocin (OT) or placebo. The Investigational Drug Service (IDS) will use a random number generator to prepare a randomization table. Participants will be block randomized by risk status at enrollment in the Mood, Mother and Infant (MMI) study, as verified by structured clinical diagnostic interview (No history of depression or anxiety, Past depression or anxiety, current depression or anxiety). Both participants and study personnel will be blinded to allocation group. At the end of the protocol, participants will be asked which condition they believed they were in ('oxytocin,' 'control,' 'not sure') to ascertain success of blinding. Forty minutes after treatment, women will undergo the Trier Social Stress Test (TSST), comprised of a speech task and a math task; the TSST reliably induces large and consistent HPA and cardiovascular responses. The TSST is administered as follows: Pre-Task Instructions: (5 minutes) Subjects will be introduced to 3 people (the 'selection committee') and asked to assume the role of a job applicant. Anticipation Period: The subject prepares her speech for 3 minutes in the presence of the committee. Speech: The committee asks the subject to deliver her talk for 5 minutes while being video and audio-recorded. If the subject finishes early, the committee responds with prepared questions to ensure that she speaks for the entire 5 minutes. These questions are designed to be non-harassing but to create a feeling of lack of predictability/controllability (e.g., "Do you have any enemies?") Serial Subtraction (PASST): The committee will ask the subject to subtract the number 7 from 2000 as quickly and accurately as possible for 5 minutes. For each mistake, the committee says "Stop -- mistake -- start over at 2000." Stress Recovery: The subject sits quietly alone for 20 minutes.

Blood will be collected at baseline, during the speech and math tasks, and at 10 and 20 minutes of recovery, as HPA-axis responses are reliably found 10-30 minutes following the TSST. Evidence regarding optimal timing of stress testing is conflicting. Visits will be scheduled for 1 pm to increase likelihood of detecting a stress response unopposed by the circadian influence, based on the experience of investigators in our laboratory and published studies of postpartum women. These investigators have found menstrual cycle phase does not affect TSST results; therefore, the date of last menstrual period and hormone use will be recorded, but visits will not be scheduled based on cycle phase.

Conditions

Depression, Postpartum; Anxiety Disorders; Stress, Psychological

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Intranasal Oxytocin

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).

Group Type: EXPERIMENTAL

Intranasal Oxytocin

Intervention Type: DRUG

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

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Intranasal Oxytocin

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Syntocinon; Inactive

Eligibility Criteria

Inclusion Criteria

1. Singleton pregnancy;

2. Intention to breastfeed (due to the centrality of breastfeeding to the oxytocin assessment);

3. Intention to remain within 40 miles of the University of North Carolina - Chapel Hill through infant's first birthday;

4. Ability to communicate in English.

Exclusion Criteria

1. 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.

2. Active substance abuse at enrollment in the 3rd trimester of pregnancy (Tobacco, alcohol, illicit substances);

3. Major congenital anomaly;

4. Chronic medication/medical condition contraindicated for breastfeeding;

5. 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alison M Stuebe, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

University of North Carolina School of Medicine

Chapel Hill, North Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37883133 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://mmi.web.unc.edu

Mood, mother and infant study web site

Other Identifiers

R01HD093901-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

12-2061

Identifier Type: -

Identifier Source: org_study_id