Estrogen and Fear in PTSD
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|ClinicalTrials.gov Identifier: NCT04192266|
Recruitment Status : Recruiting
First Posted : December 10, 2019
Last Update Posted : June 30, 2021
|Condition or disease||Intervention/treatment||Phase|
|PTSD||Drug: Estradiol Drug: Placebo oral tablet||Phase 3|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Care Provider)|
|Masking Description:||double blinded|
|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|
|Actual Study Start Date :||June 24, 2020|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||December 2022|
Experimental: Prolonged Exposure (PE) therapy with estradiol
A 2.0 mg pill of estradiol (a form of estrogen) together with prolonged exposure (PE) therapy can improve this treatment outcome in women diagnosed with Post-Traumatic Stress Disorder (PTSD). Prolonged Exposure (PE) therapy is a validated treatment for PTSD. A single dose of estradiol 2mg or placebo will be taken at home by the study participant 5-6 hours before each of 5 PE treatment sessions (sessions 2 to 6)
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)
Other Name: Estrace
Placebo Comparator: Prolonged Exposure (PE) therapy with placebo
A 2.0 mg placebo pill will be given with prolonged exposure (PE) therapy can improve this treatment outcome in women diagnosed with Post-Traumatic Stress Disorder (PTSD). Prolonged Exposure (PE) therapy is a validated treatment for PTSD.
Drug: 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)
- Change from Baseline on extinction-induced functional MRI responses. [ Time Frame: Visit 1-3 (Day 1-3) ]The outcome measure is brain activation within fear extinction network.
- Change from Baseline on PTSD symptom severity [ Time Frame: Visit 13 -15 (1, 3, and 6 months follow up) ]The outcome measure is change in PTSD severity as indexed by CAPS scores.
- Changes from Baseline in PTSD symptoms correlations with Bold and SCR changes [ Time Frame: Visit 1-3 (Day 1-3) ]The degree of PTSD symptom reduction post- compared to pre-PE after 3 weeks of treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04192266
|Contact: Mohammed R Milad, PhD||646-754-7046||Mohammed.firstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pennsylvania Perelman School of Medicine||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Edna Foa, PhD 215-746-3327 email@example.com|
|Principal Investigator:||Mohammed R Milad, PhD||NYU Langone Health|