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The purpose of the study is to use fMRI to investigate amygdala response to fearful faces in men and women with and without PTSD who have experienced childhood trauma. The study will also compare the effects of oxytocin and placebo on amygdala response, and explore the interaction of oxytocin plasma levels and amygdala response in men and women with and without PTSD who have experienced childhood trauma.
Hypothesis 1: Amygdala responding will be greater in subjects with PTSD as compared to resilient subjects, and no sex differences in the magnitude of the response will be found.
Hypothesis 2A: In response to OT, women will exhibit a greater reduction in amygdala responding than men.
Hypothesis 2B: In response to OT, women with PTSD will exhibit a greater reduction in amygdala responding compared to women without PTSD.
Hypothesis 3A: Women with PTSD will have lower levels of plasma OT as compared to men with PTSD, and women and men without PTSD.
Hypothesis 3B: Plasma OT levels will be inversely correlated with amygdala responding to fearful faces in women but not in men.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PTSD placebo Day 1, Oxytocin Day 2 | Placebo Comparator | Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). |
|
| PTSD Oxytocin Day 1, Placebo Day 2 | Experimental | Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). |
|
| Resilient Placebo Day 1, Oxytocin Day 2 | Placebo Comparator | Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). |
|
| Resilient Oxytocin Day 1, Placebo Day 2 | Experimental | Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m.on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxytocin | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Amygdala Activation- Oxy Minus Placebo | Bold signal response to facial recognition task was contrasted between oxytocin and saline administrations. Participants with PTSD and Resilient Controls each underwent 2 sets of scanning procedures, one with placebo and one with Oxytocin. Participants were randomly assigned to received Oxytocin on Day 1 or Day 2, and placebo on the opposite day, to mitigate crossover effects. Outcome measure is change in bold signal response between the two days; bold signal response on placebo was subtracted from bold signal response on Oxytocin to obtain change score. | Days 1 and 2 |
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Inclusion Criteria
Exclusion Criteria
1. Subjects must meet DSM-IV criteria for current (i.e. last 6 months) PTSD. 2. Subjects may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria) or other anxiety disorders (panic disorder, agoraphobia, social phobia, generalized anxiety disorder, or obsessive compulsive disorder) or past (>90 days) alcohol dependence. The inclusion of subjects with affective and other anxiety disorders is essential because of the marked frequency of the co-existence of mood and other anxiety disorders among patients with PTSD (Brady, Killeen, Brewerton, & Lucerini, 2000; Kessler, Chiu, Demler, Merikangas, & Walters, 2005).
Exclusion Criteria
1. As above. Exclusion Criteria
1. Subjects meeting criteria for current or past (i.e. last 90 days) Axis I mood or anxiety disorders (including PTSD and depression).
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| Name | Affiliation | Role |
|---|---|---|
| Megan Moran- Santa Maria, PhD | Medical University of South Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Neurosciences Division-Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34455213 | Derived | Sippel LM, Flanagan JC, Holtzheimer PE, Moran-Santa-Maria MM, Brady KT, Joseph JE. Effects of intranasal oxytocin on threat- and reward-related functional connectivity in men and women with and without childhood abuse-related PTSD. Psychiatry Res Neuroimaging. 2021 Nov 30;317:111368. doi: 10.1016/j.pscychresns.2021.111368. Epub 2021 Aug 20. |
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Participants were recruited primarily through media advertisements and flyers.
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| ID | Title | Description |
|---|---|---|
| FG000 | PTSD Placebo Day 1, Oxytocin Day 2 | Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo |
| FG001 | PTSD Oxytocin Day 1, Placebo Day 2 | Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin |
| FG002 | Resilient Placebo Day 1, Oxytocin Day 2 | Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo |
| FG003 | Resilient Oxytocin Day 1, Placebo Day 2 | Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | PTSD Placebo Day 1, Oxytocin Day 2 | Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Change in Amygdala Activation- Oxy Minus Placebo | Bold signal response to facial recognition task was contrasted between oxytocin and saline administrations. Participants with PTSD and Resilient Controls each underwent 2 sets of scanning procedures, one with placebo and one with Oxytocin. Participants were randomly assigned to received Oxytocin on Day 1 or Day 2, and placebo on the opposite day, to mitigate crossover effects. Outcome measure is change in bold signal response between the two days; bold signal response on placebo was subtracted from bold signal response on Oxytocin to obtain change score. | Population analyzed are participants who completed both scans and had usable MRI data. | Posted | Mean | Standard Deviation | percentage of BOLD signal change | Days 1 and 2 |
|
Adverse events were collected for each participant under both conditions, placebo and Oxytocin. Adverse events are reported summarily for each group.
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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 | PTSD Placebo | Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Megan Moran-Santa Maria | MUSC | 843-817-6233 | moranm@musc.edu |
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| ID | Term |
|---|---|
| D013313 | Stress Disorders, Post-Traumatic |
| ID | Term |
|---|---|
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D010121 | Oxytocin |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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|
| Placebo | Drug |
|
|
| BG001 | PTSD Oxytocin Day 1, Placebo Day 2 | Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin |
| BG002 | Resilient Placebo Day 1, Oxytocin Day 2 | Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo |
| BG003 | Resilient Oxytocin Day 1, Placebo Day 2 | Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | Count of Participants |
|
| OG001 | PTSD Oxytocin Day 1, Placebo Day 2 | Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin |
| OG002 | Resilient Placebo Day 1, Oxytocin Day 2 | Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo |
| OG003 | Resilient Oxytocin Day 1, Placebo Day 2 | Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin |
|
|
| 0 |
| 19 |
| 0 |
| 19 |
| 0 |
| 19 |
| EG001 | PTSD Oxytocin | Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin | 0 | 19 | 0 | 19 | 0 | 19 |
| EG002 | Resilient Placebo | Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo | 0 | 19 | 0 | 19 | 0 | 19 |
| EG003 | Resilient Oxytocin | Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin | 0 | 19 | 0 | 19 | 0 | 19 |
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| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |