PTSDPhase 3NCT04192266
Estrogen and Fear in PTSD
A Phase 3 study testing Estradiol and Prolonged Exposure (PE) therapy in people with PTSD, run by The University of Texas Health Science Center, Houston at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- PTSD
- What is being tested?
- Estradiol and Prolonged Exposure (PE) therapy
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 83 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Jun 2020to 2 Dec 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Female, 18-45 years of age
- 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.)
- CAPS-5 Past Month score ≥ 20
- Criterion A traumatic event
- Stable medications for 3 or more months by the time of study entrance (with the exception of benzodiazepines)
- 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.
- Willing and able to provide informed consent
Who cannot join
- Diagnosis of bipolar I disorder with a past year manic episode
- 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.
- 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.
- Cognitive impairment that would interfere with the ability to focus on posttraumatic stress disorder (PTSD) in clinic, as determined by clinical judgment.
- 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).
- Suicidal ideation with imminent risk that warrants a higher level of care.
Show all 13Show fewer
- Concurrent trauma focused psychotherapy
- Pregnancy (to be ruled out by urine ß-HCG).
- 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).
- History of breast cancer or hormone-responsive cancer.
- Use of benzodiazepines
- Self-injurious behavior that involves suicidal intent, requires medical attention, or occurs daily.
- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The University of Texas Health Science Center at Houston (UTHealth Houston)
Houston, Texas, 77054
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Randomized, Double-blind Placebo-controlled Multi-center Study of Identifying Neural Mechanisms of PTSD Symptom Reduction Induced by Combined Estrogen and Prolonged Exposure Therapy
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.
Read the 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.
- Conditions
- PTSD
- Being tested
- Estradiol, Placebo oral tablet, Prolonged Exposure (PE) therapy
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Also called Estrace
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)
Placebo oral tabletDrug
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) therapyBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Estradiol; Behavioral: Prolonged Exposure (PE) therapy |
| 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. Receives: Drug: Placebo oral tablet; Behavioral: Prolonged Exposure (PE) therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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.
Measured: Before and after treatment on Experimental day 2
Secondary outcomes (5)
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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline, 6 months post intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2019
- Study start24 Jun 2020
- Primary completion29 May 2024
- Study completion2 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PTSDStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Mohammed Milad, The University of Texas Health Science Center, Houston
- Investigators
- Mohammed R Milad, PhD, Principal investigator, The University of Texas Health Science Center at Houston (UTHealth Houston)Mohammed R Milad, PhD, Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04192266
- Sponsor's protocol ID
- HSC-MS-23-0497
- Other IDs
- R33MH111907
- Status last verified
- Jan 2026
- First submitted
- 17 Oct 2019
- Last updated
- 9 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind Placebo-controlled Multi-center Study of Identifying Neural Mechanisms of PTSD Symptom Reduction Induced by Combined Estrogen and Prolonged Exposure Therapy
- ClinicalTrials.gov ID
- NCT04192266
- Acronym / sponsor ID
- HSC-MS-23-0497
- Conditions
- PTSD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 24 Jun 2020 (actual)
- Primary completion
- 29 May 2024 (actual)
- Study completion
- 2 Dec 2024 (actual)
- First posted
- 10 Dec 2019 (actual)
- Results
- Posted 9 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prolonged Exposure (PE) therapy with Estradiol | Experimental | Drug: Estradiol, Behavioral: Prolonged Exposure (PE) therapyA 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 | Drug: Placebo oral tablet, Behavioral: Prolonged Exposure (PE) therapyA 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Female, 18-45 years of age
- 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.)
- CAPS-5 Past Month score ≥ 20
- Criterion A traumatic event
- Stable medications for 3 or more months by the time of study entrance (with the exception of benzodiazepines)
Key exclusion criteria (13 listed)
- Diagnosis of bipolar I disorder with a past year manic episode
- 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.
- 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.
- Cognitive impairment that would interfere with the ability to focus on posttraumatic stress disorder (PTSD) in clinic, as determined by clinical judgment.
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EstradiolAlso: Estrace2.0 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) | Drug | Prolonged Exposure (PE) therapy with Estradiol |
| Placebo oral tablet2.0 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) | Drug | Prolonged Exposure (PE) therapy with Placebo |
| Prolonged Exposure (PE) therapyThere 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. | Behavioural | Prolonged Exposure (PE) therapy with Estradiol, Prolonged Exposure (PE) therapy with Placebo |
Primary outcome
Change in Amygdala Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
5 secondary outcomes
Skin Conductance Response (SCR) During Recall
Time frame: Pre - Treatment Experimental Day 2 recall
Skin Conductance Response (SCR) During Recall
Time frame: Post- Treatment Experimental Day 2 recall
Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS)
Time frame: Baseline, 1 month post intervention
Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS)
Time frame: Baseline, 3 months post intervention
Change in PTSD Symptom Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS)
Time frame: Baseline, 6 months post intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohammed R Milad, PhD principal investigator
The University of Texas Health Science Center at Houston (UTHealth Houston)
Mohammed R Milad, PhD principal investigator
The University of Texas Health Science Center, Houston
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Estradiol and Prolonged Exposure (PE) therapy in people with PTSD, run by The University of Texas Health Science Center, Houston at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Amygdala Activation as Measured by Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) Signal (time frame: Before and after treatment on Experimental day 2). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026.