| ID | Type | Description | Link |
|---|---|---|---|
| R33MH111907 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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The purpose of this research study is to determine if taking a pill of estradiol (E2) together with prolonged exposure (PE) therapy can improve this treatment outcome in women diagnosed with Post-Traumatic Stress Disorder (PTSD). 80 subjects will take part in this research study across UTHealth Houston and UPenn (40 subjects at each site). Participants will be randomized into one of two groups, PE + E2 or PE + placebo. The study will include preliminary screening and baseline visits, experimental visits, and therapy visits over the course of six weeks. Several follow-up visits will take place.
Prolonged-exposure (PE) therapy is the treatment of choice for posttraumatic stress disorder (PTSD). Despite its efficacy, a significant number of individuals will not benefit from it or might drop out before the completion of all sessions. This underlies the importance of findings ways to enhance the efficacy of PE in order to improve the life quality of individuals suffering from PTSD. It is now widely accepted that extinction learning paradigms used in fundamental studies are useful laboratory analogs to PE. Studies in healthy controls have suggested that elevated estrogen levels benefit extinction learning by promoting its consolidation and thus enhancing its recall when tested later for it. This is also being reflected by changes in the activation of brain regions forming the fear extinction network, including the amygdala, dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC). It is still unknown whether estradiol (E2) administration can modulate the activation of the fear extinction network in oral contraceptive (OC) users and which E2 dose could yield the best results. During the R61 phase of the study, we found that both doses of E2 were effective in engaging the functional activation of the fear extinction network. Therefore, we will use the lower dose (2mg) for the R33 phase. We will combine E2 administration with PE sessions to see if administration of PE can significantly improve clinical outcomes (reduced PTSD symptoms) and engage the fear extinction network in the brain.
Hypothesis: A general improvement is expected after 3 weeks of treatment in both groups given the anticipated benefits of PE alone. But the benefit of the Estradiol-treated groups is hypothesized be larger; with this group exhibiting significantly higher activation in brain regions associated with fear extinction. This will be noted at the follow-up scan compared to the baseline scan.
PTSD symptom severity expected be significantly lower in the Estradiol and PE group relative to the Placebo+PE group following acute treatment after three weeks of treatment.
The degree of PTSD symptom reduction post- compared to pre-PE after 3 weeks of treatment is expected be associated with BOLD changes in the fear extinction network and reduction in SCR during the extinction recall test after PE. The magnitude of BOLD and SCR changes will be significantly larger in the E2+PE group compared to the Plc+PE group.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prolonged Exposure (PE) therapy with Estradiol | Experimental | A single 2mg dose of estradiol (a form of estrogen) will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. |
|
| Prolonged Exposure (PE) therapy with Placebo | Placebo Comparator | A single 2mg placebo pill will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Estradiol | Drug | 2.0 mg of estradiol will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions (Session 2- 6) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Amygdala Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Functional Magnetic Resonance Imaging (fMRI) will be used to assess Blood Oxygen Level Dependent (BOLD) signal activation in the amygdala before and after completion of the experimental task. Change in activation will be reported using beta weights; positive beta weights mean greater activation and negative beta weights mean less activation in the specific brain region being monitored | Before and after treatment on Experimental day 2 |
| Change in Dorsal Anterior Cingulate Cortex (dACC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Functional Magnetic Resonance Imaging (fMRI) will be used to assess Blood Oxygen Level Dependent (BOLD) signal activation in the dorsal anterior cingulate cortex (dACC) before and after completion of the experimental task. Change in activation will be reported using beta weights; positive beta weights mean greater activation and negative beta weights mean less activation in the specific brain region being monitored | Before and after treatment on Experimental day 2 |
| Change in Ventromedial Prefrontal Cortex (vmPFC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Functional Magnetic Resonance Imaging (fMRI) will be used to assess Blood Oxygen Level Dependent (BOLD) signal activation in the ventromedial prefrontal cortex (vmPFC) before and after completion of the experimental task. Change in activation will be reported using beta weights; positive beta weights mean greater activation and negative beta weights mean less activation in the specific brain region being monitored | Before and after treatment on Experimental day 2 |
| Change in Hippocampus Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Functional Magnetic Resonance Imaging (fMRI) will be used to assess Blood Oxygen Level Dependent (BOLD) signal activation in the hippocampus before and after completion of the experimental task. Change in activation will be reported using beta weights; positive beta weights mean greater activation and negative beta weights mean less activation in the specific brain region being monitored. |
| Measure | Description | Time Frame |
|---|---|---|
| Skin Conductance Response (SCR) During Recall | Skin Conductance Response (SCR) assesses the stress/seat level, or level of anxiety in a particular moment, or in response to a specific cue. SCR are reported in microsiemens, a positive value indicates an increase of response to the condition stimulus relative to 3 seconds prior to its onset. A negative value indicates a decrease in response to the condition stimulus relative to 3 seconds prior to its onset. |
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Inclusion Criteria:
Exclusion Criteria:
Estrogens are female sex hormones that are primarily produced by the ovaries and include estrone (E1), estradiol (E2) and estriol (E3). E2 is the predominant and most potent circulating estrogen produced during the reproductive years in non-pregnant women and is commonly prescribed in pill and transdermal form to treat postmenopausal symptoms
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| Name | Affiliation | Role |
|---|---|---|
| Mohammed R Milad, PhD | The University of Texas Health Science Center at Houston (UTHealth Houston) | Principal Investigator |
| Mohammed R Milad, PhD | The University of Texas Health Science Center, Houston | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania Perelman School of Medicine | Philadelphia | Pennsylvania | 19104 | United States | ||
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
The investigator who proposed to use the data will have access and will provide upon reasonable request.
Requests should be directed to Mohammed.R.Milad@uth.tmc.edu. To gain access, data requestors will need to sign a data access agreement.
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A total of 123 participants were screened for eligibility. Of these, 83 participants met inclusion criteria and were enrolled in the study. Among the enrolled participants, 19 withdrew before randomization. The remaining 64 participants were randomized and began study participation.
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| ID | Title | Description |
|---|---|---|
| FG000 | Prolonged Exposure (PE) Therapy With Estradiol | A single 2mg dose of estradiol (a form of estrogen) will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. Estradiol: 2.0 mg of estradiol will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions (Session 2- 6) Prolonged Exposure (PE) therapy: There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life. |
| FG001 | Prolonged Exposure (PE) Therapy With Placebo | A single 2mg placebo pill will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. Placebo oral tablet: 2.0 mg placebo pills will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions ( Sessions 2-6) Prolonged Exposure (PE) therapy: There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Prolonged Exposure (PE) Therapy With Estradiol | A single 2mg dose of estradiol (a form of estrogen) will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. Estradiol: 2.0 mg of estradiol will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions (Session 2- 6) Prolonged Exposure (PE) therapy: There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life. |
| 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 as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Functional Magnetic Resonance Imaging (fMRI) will be used to assess Blood Oxygen Level Dependent (BOLD) signal activation in the amygdala before and after completion of the experimental task. Change in activation will be reported using beta weights; positive beta weights mean greater activation and negative beta weights mean less activation in the specific brain region being monitored | Data were not collected from 4 participants in the Prolonged Exposure (PE) Therapy With Active Pill arm because 3 participants dropped out and 1 participant had data acquisition errors. Data were not collected from 3 participants in the Prolonged Exposure (PE) Therapy With Placebo arm because 2 participants dropped out and 1 participant experienced an adverse event and the visit was not completed. | Posted | Mean | Standard Error | beta weights | Before and after treatment on Experimental day 2 |
|
Up to 6 months
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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 | Prolonged Exposure (PE) Therapy With Estradiol | A single 2mg dose of estradiol (a form of estrogen) will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. Estradiol: 2.0 mg of estradiol will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions (Session 2- 6) Prolonged Exposure (PE) therapy: There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea and/or vomiting and/or diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mohammed R Milad, PhD | The University of Texas Health Science Center at Houston | 713-486-2754 | Mohammed.R.Milad@uth.tmc.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 | Mar 4, 2025 | Dec 1, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 12, 2024 | Dec 1, 2025 | ICF_001.pdf |
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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 |
|---|---|
| D004958 | Estradiol |
| D013812 | Therapeutics |
| ID | Term |
|---|---|
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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double blinded
|
| Placebo oral tablet | Drug | 2.0 mg placebo pills will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions ( Sessions 2-6) |
|
| Prolonged Exposure (PE) therapy | Behavioral | There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life. |
|
| Before and after treatment on Experimental day 2 |
| Pre - Treatment Experimental Day 2 recall |
| Skin Conductance Response (SCR) During Recall | Skin Conductance Response (SCR) assesses the stress/seat level, or level of anxiety in a particular moment, or in response to a specific cue. SCR will be reported in microsiemens | Post- Treatment Experimental Day 2 recall |
| Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | The Clinician-Administered PTSD Scale for DSM-5 (CAPS) measures PTSD symptom severity. CAPS has a total score from 0 to 80, with higher scores indicating more severe PTSD symptoms. The change in score will be reported as the [(Score at 1 month post intervention) - (Score at Baseline)] - A negative value indicates a reduction in PTSD symptom severity | Baseline, 1 month post intervention |
| Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | The Clinician-Administered PTSD Scale for DSM-5 (CAPS) measures PTSD symptom severity. CAPS has a total score from 0 to 80, with higher scores indicating more severe PTSD symptoms. The change in score will be reported as the [(Score at 3 month post intervention) - (Score at Baseline)] - A negative value indicates a reduction in PTSD symptom severity | Baseline, 3 months post intervention |
| Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | The Clinician-Administered PTSD Scale for DSM-5 (CAPS) measures PTSD symptom severity. CAPS has a total score from 0 to 80, with higher scores indicating more severe PTSD symptoms. The change in score will be reported as the [(Score at 6 month post intervention) - (Score at Baseline)] - A negative value indicates a reduction in PTSD symptom severity | Baseline, 6 months post intervention |
| The University of Texas Health Science Center at Houston (UTHealth Houston) |
| Houston |
| Texas |
| 77054 |
| United States |
| BG001 | Prolonged Exposure (PE) Therapy With Placebo | A single 2mg placebo pill will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. Placebo oral tablet: 2.0 mg placebo pills will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions ( Sessions 2-6) Prolonged Exposure (PE) therapy: There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Marital Status | Count of Participants | Participants |
|
| Highest Education Level Completed | Count of Participants | Participants |
|
| Current Employment Status | Count of Participants | Participants |
|
| Prolonged Exposure (PE) Therapy With Estradiol |
A single 2mg dose of estradiol (a form of estrogen) will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. Estradiol: 2.0 mg of estradiol will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions (Session 2- 6) Prolonged Exposure (PE) therapy: There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life. |
| OG001 | Prolonged Exposure (PE) Therapy With Placebo | A single 2mg placebo pill will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. Placebo oral tablet: 2.0 mg placebo pills will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions ( Sessions 2-6) Prolonged Exposure (PE) therapy: There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life. |
|
|
| Primary | Change in Dorsal Anterior Cingulate Cortex (dACC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Functional Magnetic Resonance Imaging (fMRI) will be used to assess Blood Oxygen Level Dependent (BOLD) signal activation in the dorsal anterior cingulate cortex (dACC) before and after completion of the experimental task. Change in activation will be reported using beta weights; positive beta weights mean greater activation and negative beta weights mean less activation in the specific brain region being monitored | Data were not collected from 4 participants in the Prolonged Exposure (PE) Therapy With Active Pill arm because 3 participants dropped out and 1 participant had data acquisition errors. Data were not collected from 3 participants in the Prolonged Exposure (PE) Therapy With Placebo arm because 2 participants dropped out and 1 participant experienced an adverse event and the visit was not completed. | Posted | Mean | Standard Error | beta weights | Before and after treatment on Experimental day 2 |
|
|
|
| Primary | Change in Ventromedial Prefrontal Cortex (vmPFC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Functional Magnetic Resonance Imaging (fMRI) will be used to assess Blood Oxygen Level Dependent (BOLD) signal activation in the ventromedial prefrontal cortex (vmPFC) before and after completion of the experimental task. Change in activation will be reported using beta weights; positive beta weights mean greater activation and negative beta weights mean less activation in the specific brain region being monitored | Data were not collected from 4 participants in the Prolonged Exposure (PE) Therapy With Active Pill arm because 3 participants dropped out and 1 participant had data acquisition errors. Data were not collected from 3 participants in the Prolonged Exposure (PE) Therapy With Placebo arm because 2 participants dropped out and 1 participant experienced an adverse event and the visit was not completed. | Posted | Mean | Standard Error | beta weights | Before and after treatment on Experimental day 2 |
|
|
|
| Primary | Change in Hippocampus Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Functional Magnetic Resonance Imaging (fMRI) will be used to assess Blood Oxygen Level Dependent (BOLD) signal activation in the hippocampus before and after completion of the experimental task. Change in activation will be reported using beta weights; positive beta weights mean greater activation and negative beta weights mean less activation in the specific brain region being monitored. | Data were not collected from 4 participants in the Prolonged Exposure (PE) Therapy With Active Pill arm because 3 participants dropped out and 1 participant had data acquisition errors. Data were not collected from 3 participants in the Prolonged Exposure (PE) Therapy With Placebo arm because 2 participants dropped out and 1 participant experienced an adverse event and the visit was not completed. | Posted | Mean | Standard Error | beta weights | Before and after treatment on Experimental day 2 |
|
|
|
| Secondary | Skin Conductance Response (SCR) During Recall | Skin Conductance Response (SCR) assesses the stress/seat level, or level of anxiety in a particular moment, or in response to a specific cue. SCR are reported in microsiemens, a positive value indicates an increase of response to the condition stimulus relative to 3 seconds prior to its onset. A negative value indicates a decrease in response to the condition stimulus relative to 3 seconds prior to its onset. | Data were not collected from 13 participants in the Prolonged Exposure (PE) Therapy With Active Pill arm because 3 participants dropped out, 5 participants had data acquisition errors, and 5 participants had unusable data. Data were not collected from 11 participants in the Prolonged Exposure (PE) Therapy With Placebo arm because 2 dropped out, 2 had data acquisition errors, 1 participant experienced an adverse event and the visit was not completed, and 6 participants had unusable data. | Posted | Mean | Standard Deviation | microsiemens | Pre - Treatment Experimental Day 2 recall |
|
|
|
| Secondary | Skin Conductance Response (SCR) During Recall | Skin Conductance Response (SCR) assesses the stress/seat level, or level of anxiety in a particular moment, or in response to a specific cue. SCR will be reported in microsiemens | Data were not collected from 13 participants in the Prolonged Exposure (PE) Therapy With Active Pill arm because 3 participants dropped out, 5 participants had data acquisition errors, and 5 participants had unusable data. Data were not collected from 11 participants in the Prolonged Exposure (PE) Therapy With Placebo arm because 2 dropped out, 2 had data acquisition errors, 1 participant experienced an adverse event and the visit was not completed, and 6 participants had unusable data. | Posted | Mean | Standard Deviation | microsiemens | Post- Treatment Experimental Day 2 recall |
|
|
|
| Secondary | Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | The Clinician-Administered PTSD Scale for DSM-5 (CAPS) measures PTSD symptom severity. CAPS has a total score from 0 to 80, with higher scores indicating more severe PTSD symptoms. The change in score will be reported as the [(Score at 1 month post intervention) - (Score at Baseline)] - A negative value indicates a reduction in PTSD symptom severity | Data were not collected from 7 participants in the PE therapy with Estradiol arm: 2 dropped out, 2 are missing baseline and post treatment scores because CAPS was not part of the study at the time and 2 are missing baseline scores because CAPS was not part of the study at this time. Data were not collected from 3 participants in the PE therapy with Placebo arm: 2 dropped out and 1 is missing both baseline and post treatment scores because CAPS measure was not part of the study at that time. | Posted | Mean | Standard Error | score on a scale | Baseline, 1 month post intervention |
|
|
|
| Secondary | Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | The Clinician-Administered PTSD Scale for DSM-5 (CAPS) measures PTSD symptom severity. CAPS has a total score from 0 to 80, with higher scores indicating more severe PTSD symptoms. The change in score will be reported as the [(Score at 3 month post intervention) - (Score at Baseline)] - A negative value indicates a reduction in PTSD symptom severity | Data were not collected from 8 participants in the PE therapy with Estradiol arm: 3 dropped out, 4 are missing baseline scores because CAPS was not part of the study at this time and 1 did not complete the 3 month follow up visit. Data were not collected from 3 participants in the PE therapy with Placebo arm: 2 dropped out and 1 is missing baseline scores because CAPS measure was not part of the study at that time. | Posted | Mean | Standard Error | score on a scale | Baseline, 3 months post intervention |
|
|
|
| Secondary | Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | The Clinician-Administered PTSD Scale for DSM-5 (CAPS) measures PTSD symptom severity. CAPS has a total score from 0 to 80, with higher scores indicating more severe PTSD symptoms. The change in score will be reported as the [(Score at 6 month post intervention) - (Score at Baseline)] - A negative value indicates a reduction in PTSD symptom severity | Data were not collected from 8 participants in the PE therapy with Estradiol arm: 3 dropped out, 4 are missing baseline scores because CAPS was not part of the study at this time and 1 did not complete the 6 month follow up visit. Data were not collected from 4 participants in the PE therapy with Placebo arm: 2 dropped out and 1 is missing baseline scores because CAPS measure was not part of the study at that time and 1 did not complete the 6 month follow up visit. | Posted | Mean | Standard Error | score on a scale | Baseline, 6 months post intervention |
|
|
|
| 0 |
| 31 |
| 0 |
| 31 |
| 17 |
| 31 |
| EG001 | Prolonged Exposure (PE) Therapy With Placebo | A single 2mg placebo pill will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD. Placebo oral tablet: 2.0 mg placebo pills will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions ( Sessions 2-6) Prolonged Exposure (PE) therapy: There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life. | 0 | 33 | 0 | 33 | 18 | 33 |
| COVID illness or post COVID vaccine symptoms | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | COVID illness or post COVID vaccine symptoms (e.g., ache arm, headache, body ache, prolonged menstruation) |
|
| Emotional distress, fatigue | Psychiatric disorders | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Issues related to menstrual cycle | Reproductive system and breast disorders | Systematic Assessment | Issues related to menstrual cycle (e.g., menstrual cramps, spotting, etc.) |
|
| Arm bruising and ache | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | Systematic Assessment | Injury (e.g. work accident, non-suicidal self-injury) |
|
| General distress due to Interpersonal Conflict | Social circumstances | Systematic Assessment |
|
| Changes in libido | Reproductive system and breast disorders | Systematic Assessment |
|
| Weight gain | General disorders | Systematic Assessment |
|
| Polyp in uterus found after routine medical checkup | Reproductive system and breast disorders | Systematic Assessment |
|
| Concussion | Nervous system disorders | Systematic Assessment |
|
| Allergic Reaction | General disorders | Systematic Assessment |
|
| Body aches | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Brain fog and nausea | Nervous system disorders | Systematic Assessment |
|
| Fever, nausea, and insomnia | General disorders | Systematic Assessment |
|
| Gastrointestinal illness | Gastrointestinal disorders | Systematic Assessment |
|
| Lymphangitis | Immune system disorders | Systematic Assessment |
|
| Neck pain | General disorders | Systematic Assessment |
|
| Tremulousness, headache, nausea | Nervous system disorders | Systematic Assessment |
|
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D011083 |
| Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |