Estrogen and Fear (PTSD)

Healthy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03371654
• Other study ID #: 2017-0689
• Status: Recruiting
• Phase: Phase 1
• Start date: June 24, 2020
• Est. completion date: November 2022

Study information

• Verified date: July 2020
• Source: NYU Langone Health
• Contact: Mohammed R Milad, PhD
• Phone: 646-754-7046
• Email: Mohammed.milad[@]nyulangone.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 80 subjects will take part in this research study across NYU Langone Health 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: November 2022
• Est. primary completion date: November 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Female, 18-45 years of age

2. Chronic (at least three months post-trauma) DSM-5 PTSD symptoms

3. CAPS-5 score = 26

4. Criterion A traumatic event

5. Symptoms include at least one re-experiencing symptom, at least one avoidance symptom, at least two cognition and mood symptoms, and at least two hyperarousal symptoms

6. Right-handed (Edinburgh Inventory - Oldfield 1971).

7. Literate in English

8. Psychiatric medications (with the exception of benzodiazepines) will be allowed if stable for at least 3 months prior to study baseline. Benzodiazepine use will be excluded.

9. Women on oral contraceptives, specifically those using monophasic of first, second, third or fourth generation with 20mcg of ethinyl estradiol or willingness to start taking oral contraceptives

10. Willing and able to provide informed consent

Exclusion Criteria:

1. Other primary diagnoses (e.g., pervasive developmental disorders, psychotic disorder, thought disorder, conduct disorder, or presence of other disorder that is primary relative to PTSD)

2. Suicidal ideation with intent

3. Concurrent trauma focused psychotherapy

4. Pregnancy (to be ruled out by urine ß-HCG).

5. Metallic implants or devices contraindicating magnetic resonance imaging.

6. History of breast cancer or hormone-responsive cancer.

7. Allergy to peanut oil.

Related Conditions & MeSH terms

• Healthy
• Stress Disorders, Post-Traumatic

Intervention

Drug:
• 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)
• Placebo
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)

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
NYU Langone Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline on extinction-induced functional MRI responses.	The outcome measure is brain activation within fear extinction network.	Visit 1-3 (Day 1-3)
Secondary	Change from Baseline on PTSD symptom severity	The outcome measure is change in PTSD severity as indexed by CAPS scores.	Visit 13 -15 (1, 3, and 6 months follow up)
Secondary	Changes from Baseline in PTSD symptoms correlations with Bold and SCR changes	The degree of PTSD symptom reduction post- compared to pre-PE after 3 weeks of treatment	Visit 1-3 (Day 1-3)