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| ID | Type | Description | Link |
|---|---|---|---|
| R01HD093901-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intranasal Oxytocin | Drug | Six intranasal sprays of oxytocin. Each insufflation delivers 4 IUs of oxytocin for a total oxytocin dosage of 24 IUs. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Adrenocorticotropic Hormone (ACTH ) During TSST | The study drug will be administered 40 minutes before the TSST. Adrenocorticotropic hormone 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Cortisol (CRT) During Trier Social Stress Test (TSST) | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on CRT during the TSST. | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes |
This study will follow-up the existing Mood, Mother and Infant (MMI) prospective longitudinal cohort (R01HD073220), comprised of 222 mother-infant dyads who were recruited between May 2013 and April 2017 and completed the 12-month MMI visit. In the MMI study, 222 mothers ages 18-45 and their infants were enrolled. Participants were recruited from community clinics in the third trimester of pregnancy and continued to participate in the study through 12 months postpartum. At the 12-month visit, mothers were invited to continue to be followed via online surveys at 6-month intervals; more than 80% of women who have completed the MMI study to date have continued to participate. Enrolled participants in the MMI study met the following inclusion and exclusion criteria:
Inclusion Criteria:
Exclusion Criteria:
At enrollment, all participants underwent a Structured Clinical Interview Non-Patient version (SCID-NP).
Inclusion Criteria for Inhaled Oxytocin and HPA Axis Reactivity, a substudy of the Psychobiology of Resilience in Mother-Child Pairs follow-up study: 1) Participated in the MMI study 2) Both mother and child willing and able to participate in the 6-year follow-up visits 3) Not pregnant, verified by urine pregnancy test on day of study visit.
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| Name | Affiliation | Role |
|---|---|---|
| Alison M Stuebe, MD, MSc | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina School of Medicine | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37883133 | Derived | 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. |
| Label | URL |
|---|---|
| Mood, mother and infant study web site | View source |
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Data will be shared according to the most recent NIH guidelines.
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).
Individual level data sharing will be subject to local IRB approval, individual written informed consents, and national law
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). Intranasal Oxytocin: Six intranasal sprays of oxytocin. Each insufflation delivers 4 IUs of oxytocin for a total oxytocin dosage of 24 IUs. |
| FG001 | 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). Placebo: Six intranasal sprays of placebo manufactured to mimic oxytocin nasal spray containing all equivalent ingredients except oxytocin. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). Intranasal Oxytocin: Six intranasal sprays of oxytocin. Each insufflation delivers 4 IUs of oxytocin for a total oxytocin dosage of 24 IUs. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Samples were collected by IV. In some participants, an IV was not able to be placed and samples could not be collected. In some participants, an IV was successfully placed, but the IV infiltrated before the end of the observation period and not all timepoints were collected. One participant had a vasovagal episode when the IV was placed and samples were not collected. All collected data are reported herein. | Posted | Mean | Standard Deviation | pg/mL | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes |
|
From the time of study drug administration through the end of the recovery period, a total of approximately 90 minutes.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). Intranasal Oxytocin: Six intranasal sprays of oxytocin. Each insufflation delivers 4 IUs of oxytocin for a total oxytocin dosage of 24 IUs. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alison Stuebe, MD, MSc | University of North Carollina at Chapel Hill | 919-966-1601 | astuebe@med.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 19, 2024 | Mar 27, 2024 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 8, 2022 | Jan 19, 2024 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D019052 | Depression, Postpartum |
| D001008 | Anxiety Disorders |
| D013315 | Stress, Psychological |
| ID | Term |
|---|---|
| D011644 | Puerperal Disorders |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D010121 | Oxytocin |
| ID | Term |
|---|---|
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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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.
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Participants will receive a nasal insufflation bottle of oxytocin intranasal spray or placebo intranasal spray manufactured to mimic oxytocin nasal spray.
|
| Placebo | Drug | Six intranasal sprays of placebo manufactured to mimic oxytocin nasal spray containing all equivalent ingredients except oxytocin. |
|
|
| Lagged Association Between ACTH and CRT During the TSST | Correlations will be quantified between ACTH at time j and CRT at time j+1 to test the extent to which CRT response is blunted by exogenous oxytocin (OT). | 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 | Recording of autonomic activity beginning prior to study drug administration (-40 minutes) until the end of recovery from the TSST (+38 minutes). Mobile Impedance Cardiographs (MindWare Tech Ltd, Gahanna, OH) was used to measure cardiac rate and interbeat interval (IBI). MindWare Heart Rate Variability (HRV) software was used to derive respiration and to calculate high frequency respiratory sinus arrhythmia power from the IBI series as an index of parasympathetic activity. Results are reported as difference from the mean of high frequency respiratory sinus arrhythmia power measured in the first ten minutes of the study visit, prior to administration of OT or placebo. | 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 | Recording of autonomic activity beginning prior to study drug administration (-40 minutes) until the end of recovery from the TSST (+38 minutes). Mobile Impedance Cardiographs (MindWare Tech Ltd, Gahanna, OH) will be used to measure pre-ejection period (PEP). PEP will index sympathetic activation. Results are reported as difference from the mean of pre-ejection period measured in the first ten minutes of the study visit, prior to administration of OT or placebo. | 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 |
| Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Adrenocorticotropic Hormone (ACTH ) During TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on ACTH during the 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 | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on 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 |
| Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on 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, 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 |
| Assessment of Effect Modification by Oxytocin Receptor (OXTR) Genotype on Changes in Cortisol (CRT) During Trier Social Stress Test (TSST) | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on CRT during the TSST. | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes |
| Assessment of Effect Modification by OXTR Genotype on Changes in Adrenocorticotropic Hormone (ACTH ) During TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on ACTH during the TSST. | -30 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes |
| Assessment of Effect Modification by OXTR Genotype Changes in High Frequency Heart Rate Variability, an Index of Parasympathetic Activity, During the TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on 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 |
| Assessment of Effect Modification by OXTR Genotype on Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on 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, 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 |
| BG001 | 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). Placebo: Six intranasal sprays of placebo manufactured to mimic oxytocin nasal spray containing all equivalent ingredients except oxytocin. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
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). Intranasal Oxytocin: Six intranasal sprays of oxytocin. Each insufflation delivers 4 IUs of oxytocin for a total oxytocin dosage of 24 IUs. |
| OG001 | 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). Placebo: Six intranasal sprays of placebo manufactured to mimic oxytocin nasal spray containing all equivalent ingredients except oxytocin. |
|
|
|
| Secondary | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | The study drug will be administered 40 minutes before the TSST. Adrenocorticotropic hormone 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). | Samples were collected by IV. In some participants, an IV was not able to be placed and samples could not be collected. In some participants, an IV was successfully placed, but the IV infiltrated before the end of the observation period and not all timepoints were collected. One participant had a vasovagal episode when the IV was placed and samples were not collected. All collected data are reported herein. | Posted | Mean | Standard Deviation | pg/mL | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes |
|
|
|
|
| Secondary | Lagged Association Between ACTH and CRT During the TSST | Correlations will be quantified between ACTH at time j and CRT at time j+1 to test the extent to which CRT response is blunted by exogenous oxytocin (OT). | Samples were collected by IV. In some participants, an IV was not able to be placed and samples could not be collected. In some participants, an IV was successfully placed, but the IV infiltrated before the end of the observation period and not all timepoints were collected. One participant had a vasovagal episode when the IV was placed and samples were not collected. All collected data are reported herein. | Posted | Number | Correlation coefficient | 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 |
|
|
|
|
| Secondary | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | Recording of autonomic activity beginning prior to study drug administration (-40 minutes) until the end of recovery from the TSST (+38 minutes). Mobile Impedance Cardiographs (MindWare Tech Ltd, Gahanna, OH) was used to measure cardiac rate and interbeat interval (IBI). MindWare Heart Rate Variability (HRV) software was used to derive respiration and to calculate high frequency respiratory sinus arrhythmia power from the IBI series as an index of parasympathetic activity. Results are reported as difference from the mean of high frequency respiratory sinus arrhythmia power measured in the first ten minutes of the study visit, prior to administration of OT or placebo. | For two participants in each arm, cardiograph recording was unsuccessful. For some time periods for some participants, data quality or quantity (in terms of lacking sufficient numbers of epochs within a period) was insufficient for analysis. All valid, analyzable data are reported herein. | Posted | Mean | Standard Deviation | ms squared | 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 |
|
|
|
|
| Secondary | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | Recording of autonomic activity beginning prior to study drug administration (-40 minutes) until the end of recovery from the TSST (+38 minutes). Mobile Impedance Cardiographs (MindWare Tech Ltd, Gahanna, OH) will be used to measure pre-ejection period (PEP). PEP will index sympathetic activation. Results are reported as difference from the mean of pre-ejection period measured in the first ten minutes of the study visit, prior to administration of OT or placebo. | For some participants in each arm, cardiograph recording was unsuccessful. For some time periods for some participants, data quality or quantity (in terms of lacking sufficient numbers of epochs within a period) was insufficient for analysis. All valid, analyzable data are reported herein. | Posted | Mean | Standard Deviation | milliseconds | 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 Pre-specified | Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Cortisol (CRT) During Trier Social Stress Test (TSST) | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on CRT during the TSST. | Not Posted | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes | Participants |
| Other Pre-specified | Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Adrenocorticotropic Hormone (ACTH ) During TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on ACTH during the TSST. | Not Posted | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes | Participants |
| Other Pre-specified | Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in High Frequency Heart Rate Variability, an Index of Parasympathetic Activity, During the TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on parasympathetic activity during the TSST. | Not Posted | 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 | Participants |
| Other Pre-specified | Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on sympathetic activity during the TSST. | Not Posted | 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 | Participants |
| Other Pre-specified | Assessment of Effect Modification by Oxytocin Receptor (OXTR) Genotype on Changes in Cortisol (CRT) During Trier Social Stress Test (TSST) | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on CRT during the TSST. | Not Posted | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes | Participants |
| Other Pre-specified | Assessment of Effect Modification by OXTR Genotype on Changes in Adrenocorticotropic Hormone (ACTH ) During TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on ACTH during the TSST. | Not Posted | -30 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes | Participants |
| Other Pre-specified | Assessment of Effect Modification by OXTR Genotype Changes in High Frequency Heart Rate Variability, an Index of Parasympathetic Activity, During the TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on parasympathetic activity during the TSST. | Not Posted | 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 | Participants |
| Other Pre-specified | Assessment of Effect Modification by OXTR Genotype on Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on sympathetic activity during the TSST. | Not Posted | 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 | Participants |
| 0 |
| 51 |
| 0 |
| 51 |
| 0 |
| 51 |
| EG001 | 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). Placebo: Six intranasal sprays of placebo manufactured to mimic oxytocin nasal spray containing all equivalent ingredients except oxytocin. | 0 | 54 | 0 | 54 | 1 | 54 |
Not provided
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| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| -20 minutes |
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| 0 minutes |
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| +10 minutes |
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| +15 minutes |
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| +28 minutes |
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| +38 minutes |
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| +48 minutes |
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| 0.92 |
| Superiority |
| T-test comparing mean ACTH by study arm at 0 minutes. | t-test, 2 sided | 0.92 | Superiority |
| T-test comparing mean ACTH by study arm at 10 minutes. | t-test, 2 sided | 0.40 | Superiority |
| T-test comparing mean ACTH by study arm at 15 minutes. | t-test, 2 sided | 0.97 | Superiority |
| T-test comparing mean ACTH by study arm at 28 minutes. | t-test, 2 sided | 0.71 | Superiority |
| T-test comparing mean ACTH by study arm at 38 minutes. | t-test, 2 sided | 0.78 | Superiority |
| T-test comparing mean ACTH by study arm at 48 minutes. | t-test, 2 sided | 0.63 | Superiority |
| A mixed effects model with random intercept and slope was used to model cortisol as the outcome variable with time, study arm, and an interaction between time and study arm as the exposure variables. This is the p-value for the interaction term between time and study arm. | Mixed Models Analysis | 0.11 | Superiority |
| ACTH at -20 minutes with 0 minutes |
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| ACTH at 0 minutes with Cortisol at +10 minutes |
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| ACTH at +10 minutes with Cortisol at +15 minutes |
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| ACTH at +15 minutes with Cortisol at +28 minutes |
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| ACTH at +28 minutes with Cortisol at +38 minutes |
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| ACTH at +38 minutes with Cortisol at +48 minutes |
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| Fisher's Z test |
| 0.22 |
| Superiority |
| Fisher's Z test for correlation between ACTH at 0 minutes and Cortisol at +10 minutes. | Fisher's Z test | 0.14 | Superiority |
| Fisher's Z test for correlation between ACTH at +10 minutes and Cortisol at +15 minutes. | Fisher's Z test | 0.14 | Superiority |
| Fisher's Z test for correlation between ACTH at +15 minutes and Cortisol at +28 minutes. | Fisher's Z test | 0.05 | Superiority |
| Fisher's Z test for correlation between ACTH at +28 minutes and Cortisol at +38 minutes. | Fisher's Z test | 0.10 | Superiority |
| Fisher's Z test for correlation between ACTH at +38 minutes and Cortisol at +48 minutes. | Fisher's Z test | 0.90 | Superiority |
| A mixed effects model with random intercept and slope was used to model cortisol at time j+1 as the outcome with ACTH at time j, study arm, and an interaction term between ACTH at time j and study arm as the exposure variables. The p-value presented below is for the interaction term between ACTH at time j and study arm. | Mixed Models Analysis | 0.21 | Superiority |
| -35 to -30 |
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| -30 to -25 |
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| -25 to -20 |
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| -20 to -15 |
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| -15 to -10 |
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| -10 to -5 |
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| -5 to 0 |
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| 5 to 8 |
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| 8 to 13 |
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| 13 to 18 |
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| 18 to 23 |
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| 23 to 28 |
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| 28 to 33 |
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| 33 to 38 |
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| 38 to 43 |
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| 43 to 48 |
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| 0.7919 |
| Superiority |
| High frequency heart rate variability at minutes -30 to -25 | t-test, 2 sided | 0.5639 | Superiority |
| High frequency heart rate variability at minutes -25 to -20 | t-test, 2 sided | 0.3139 | Superiority |
| High frequency heart rate variability at minutes -20 to -15 | t-test, 2 sided | 0.4222 | Superiority |
| High frequency heart rate variability at minutes -15 to -10 | t-test, 2 sided | 0.834 | Superiority |
| High frequency heart rate variability at minutes -10 to -5 | t-test, 2 sided | 0.7562 | Superiority |
| High frequency heart rate variability at minutes -5 to 0 | t-test, 2 sided | 0.4245 | Superiority |
| High frequency heart rate variability at minutes 5 to 8 | t-test, 2 sided | 0.1425 | Superiority |
| High frequency heart rate variability at minutes 8 to 13 | t-test, 2 sided | 0.7175 | Superiority |
| High frequency heart rate variability at minutes 13 to 18 | t-test, 2 sided | 0.1417 | Superiority |
| High frequency heart rate variability at minutes 18 to 23 | t-test, 2 sided | 0.0514 | Superiority |
| High frequency heart rate variability at minutes 23 to 28 | t-test, 2 sided | 0.1507 | Superiority |
| High frequency heart rate variability at minutes 8 to 33 | t-test, 2 sided | 0.4204 | Superiority |
| High frequency heart rate variability at minutes 33 to 38 | t-test, 2 sided | 0.4209 | Superiority |
| High frequency heart rate variability at minutes 38 to 43 | t-test, 2 sided | 0.2569 | Superiority |
| High frequency heart rate variability at minutes 43 to 48 | t-test, 2 sided | 0.0828 | Superiority |
| -35 to -30 |
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| -30 to -25 |
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| -25 to -20 |
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| -20 to -15 |
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| -15 to -10 |
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| -10 to -5 |
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| -5 to 0 |
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| 5 to 8 |
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| 8 to 13 |
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| 13 to 18 |
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| 18 to 23 |
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| 23 to 28 |
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| 28 to 33 |
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| 33 to 38 |
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| 38 to 43 |
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| 43 to 48 |
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|
| 0.3228 |
| Superiority |
| Pre-ejection period at minutes -30 to -25 | t-test, 2 sided | 0.3541 | Superiority |
| Pre-ejection period at minutes -25 to -20 | t-test, 2 sided | 0.4311 | Superiority |
| Pre-ejection period at minutes -20 to -15 | t-test, 2 sided | 0.3349 | Superiority |
| Pre-ejection period at minutes -15 to -10 | t-test, 2 sided | 0.2646 | Superiority |
| Pre-ejection period at minutes -10 to -5 | t-test, 2 sided | 0.1095 | Superiority |
| Pre-ejection period at minutes -5 to 0 | t-test, 2 sided | 0.0194 | Superiority |
| Pre-ejection period at minutes 5 to 8 | t-test, 2 sided | 0.473 | Superiority |
| Pre-ejection period at minutes 8 to 13 | t-test, 2 sided | 0.5768 | Superiority |
| Pre-ejection period at minutes 13 to 18 | t-test, 2 sided | 0.3477 | Superiority |
| Pre-ejection period at minutes 18 to 23 | t-test, 2 sided | 0.1413 | Superiority |
| Pre-ejection period at minutes 23 to 28 | t-test, 2 sided | 0.2128 | Superiority |
| Pre-ejection period at minutes 28 to 33 | t-test, 2 sided | 0.1415 | Superiority |
| Pre-ejection period at minutes 33 to 38 | t-test, 2 sided | 0.1126 | Superiority |
| Pre-ejection period at minutes 38 to 43 | t-test, 2 sided | 0.1647 | Superiority |
| Pre-ejection period at minutes 43 to 48 | t-test, 2 sided | 0.088 | Superiority |