PTSD
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGEstradiol
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)
DRUGPlacebo 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)
BEHAVIORALProlonged 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.
Sponsors
National Institute of Mental Health (NIMH)
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
double blinded
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Female, 18-45 years of age 2. Chronic (at least one month post-trauma) DSM-5 FULL PTSD diagnosis OR subPTSD diagnosis (subPTSD defined as: meeting criterion A, F, G, H, and clusters B, C, and at least 1 of the clusters D or E.) 3. CAPS-5 Past Month score ≥ 20 4. Criterion A traumatic event 5. Stable medications for 3 or more months by the time of study entrance (with the exception of benzodiazepines) 6. Women on oral contraceptives, specifically those using monophasic or biphasic of first, second, third or fourth generation with up to 35mcg of ethinyl estradiol; OR using etonogestrel / ethinyl estradiol 0.120mg/0.015mg per day vaginal ring birth control; OR using the norelgestromin / ethinyl estradiol 0.150mg/0.035mg per day transdermal patch birth control. 7. Willing and able to provide informed consent
Exclusion criteria
1. Diagnosis of bipolar I disorder with a past year manic episode 2. Diagnosis of a psychotic disorder or psychotic symptoms that would interfere with the ability to focus on posttraumatic stress disorder (PTSD) in clinic, as determined by clinical judgment. 3. Diagnosis of moderate or severe substance use disorder that would interfere with the ability to focus on posttraumatic stress disorder (PTSD) in clinic, as determined by clinical judgment. 4. Cognitive impairment that would interfere with the ability to focus on posttraumatic stress disorder (PTSD) in clinic, as determined by clinical judgment. 5. History of neurological disease (that involves the brain), seizure, or significant head trauma (i.e., extended loss of consciousness, neurological sequelae, or known structural brain lesion). 6. Suicidal ideation with imminent risk that warrants a higher level of care. 7. Concurrent trauma focused psychotherapy 8. Pregnancy (to be ruled out by urine ß-HCG). 9. Metallic implants or devices contraindicating magnetic resonance imaging by interfering with patient safety or fMRI data collection. Cases will be cleared by the Principal Investigator and/or Baylor College of Medicine (Imaging). 10. History of breast cancer or hormone-responsive cancer. 11. Use of benzodiazepines 12. Self-injurious behavior that involves suicidal intent, requires medical attention, or occurs daily. 13. High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process, based on investigator/clinician clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Amygdala Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Before and after treatment on Experimental day 2 | 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 |
| Change in Dorsal Anterior Cingulate Cortex (dACC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Before and after treatment on Experimental day 2 | 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 |
| Change in Ventromedial Prefrontal Cortex (vmPFC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Before and after treatment on Experimental day 2 | 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 |
| Change in Hippocampus Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | Before and after treatment on Experimental day 2 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Skin Conductance Response (SCR) During Recall | Pre - Treatment Experimental Day 2 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. |
| Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | Baseline, 1 month post intervention | 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 |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 31 |
| 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. | 33 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Prolonged Exposure (PE) Therapy With Estradiol | Prolonged Exposure (PE) Therapy With Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 33 Participants | 64 Participants |
| Current Employment Status Full-time employment | 11 Participants | 18 Participants | 29 Participants |
| Current Employment Status Not applicable | 5 Participants | 1 Participants | 6 Participants |
| Current Employment Status Part-time employment | 5 Participants | 6 Participants | 11 Participants |
| Current Employment Status Recipient of public/private assistance | 0 Participants | 0 Participants | 0 Participants |
| Current Employment Status Student/Dependent on spouse | 10 Participants | 8 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 29 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Highest Education Level Completed College Graduate | 11 Participants | 13 Participants | 24 Participants |
| Highest Education Level Completed Graduate School | 7 Participants | 11 Participants | 18 Participants |
| Highest Education Level Completed High School Graduate | 0 Participants | 1 Participants | 1 Participants |
| Highest Education Level Completed Junior High School | 0 Participants | 0 Participants | 0 Participants |
| Highest Education Level Completed Less than 7 years of school | 0 Participants | 0 Participants | 0 Participants |
| Highest Education Level Completed Partial College | 13 Participants | 8 Participants | 21 Participants |
| Highest Education Level Completed Partial High School | 0 Participants | 0 Participants | 0 Participants |
| Marital Status Divorced | 0 Participants | 3 Participants | 3 Participants |
| Marital Status Living with Partner | 6 Participants | 7 Participants | 13 Participants |
| Marital Status Married | 2 Participants | 3 Participants | 5 Participants |
| Marital Status Separated | 0 Participants | 0 Participants | 0 Participants |
| Marital Status Single | 23 Participants | 20 Participants | 43 Participants |
| Marital Status Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Marital Status Widowed | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized More than One Race | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 22 Participants | 41 Participants |
| Region of Enrollment United States | 31 participants | 33 participants | 64 participants |
| Sex: Female, Male Female | 31 Participants | 33 Participants | 64 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 33 |
| other Total, other adverse events | 17 / 31 | 18 / 33 |
| serious Total, serious adverse events | 0 / 31 | 0 / 33 |
Outcome results
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
Time frame: Before and after treatment on Experimental day 2
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolonged Exposure (PE) Therapy With Estradiol | Change in Amygdala Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | 0.534 beta weights | Standard Error 0.201 |
| Prolonged Exposure (PE) Therapy With Placebo | Change in Amygdala Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | -0.0037 beta weights | Standard Error 0.159 |
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
Time frame: Before and after treatment on Experimental day 2
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolonged Exposure (PE) Therapy With Estradiol | Change in Dorsal Anterior Cingulate Cortex (dACC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | 0.292 beta weights | Standard Error 0.213 |
| Prolonged Exposure (PE) Therapy With Placebo | Change in Dorsal Anterior Cingulate Cortex (dACC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | -0.0276 beta weights | Standard Error 0.219 |
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.
Time frame: Before and after treatment on Experimental day 2
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolonged Exposure (PE) Therapy With Estradiol | Change in Hippocampus Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | 0.341 beta weights | Standard Error 0.158 |
| Prolonged Exposure (PE) Therapy With Placebo | Change in Hippocampus Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | -0.0606 beta weights | Standard Error 0.178 |
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
Time frame: Before and after treatment on Experimental day 2
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolonged Exposure (PE) Therapy With Estradiol | Change in Ventromedial Prefrontal Cortex (vmPFC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | 0.512 beta weights | Standard Error 0.247 |
| Prolonged Exposure (PE) Therapy With Placebo | Change in Ventromedial Prefrontal Cortex (vmPFC) Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal | -0.118 beta weights | Standard Error 0.209 |
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
Time frame: Baseline, 6 months post intervention
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolonged Exposure (PE) Therapy With Estradiol | Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | -22.83 score on a scale | Standard Error 1.7812 |
| Prolonged Exposure (PE) Therapy With Placebo | Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | -23.62 score on a scale | Standard Error 1.9095 |
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
Time frame: Baseline, 1 month post intervention
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolonged Exposure (PE) Therapy With Estradiol | Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | -14.83 score on a scale | Standard Error 1.848 |
| Prolonged Exposure (PE) Therapy With Placebo | Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | -18.23 score on a scale | Standard Error 1.848 |
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
Time frame: Baseline, 3 months post intervention
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolonged Exposure (PE) Therapy With Estradiol | Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | -21.04 score on a scale | Standard Error 1.5572 |
| Prolonged Exposure (PE) Therapy With Placebo | Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS) | -22.3 score on a scale | Standard Error 1.8944 |
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
Time frame: Post- Treatment Experimental Day 2 recall
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolonged Exposure (PE) Therapy With Estradiol | Skin Conductance Response (SCR) During Recall | 0.000479 microsiemens | Standard Deviation 0.0167 |
| Prolonged Exposure (PE) Therapy With Placebo | Skin Conductance Response (SCR) During Recall | 0.0894 microsiemens | Standard Deviation 0.0457 |
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.
Time frame: Pre - Treatment Experimental Day 2 recall
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolonged Exposure (PE) Therapy With Estradiol | Skin Conductance Response (SCR) During Recall | -0.0741 microsiemens | Standard Deviation 0.0821 |
| Prolonged Exposure (PE) Therapy With Placebo | Skin Conductance Response (SCR) During Recall | -0.195 microsiemens | Standard Deviation 0.0659 |