Neuroendocrine Risk for PTSD in Women

NCT03973229 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: IRB001035951R01MH117009-01A1
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test for effects of estradiol (E2) on PTSD symptoms and functional magnetic resonance imaging (fMRI) indicators of stress vulnerability, in naturally-cycling women who are not using hormonal birth control. Enrollment will be targeted to create three groups within two cohorts (early follicular phase and luteal phase):

1. 1.PTSD: Women who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for PTSD
2. 2.Trauma-Exposed (TC): Women matched for age and trauma exposure severity but without PTSD
3. 3.Healthy Control (HC): Women matched for age, but without trauma history or psychiatric disorder (self-reported)

Conditions

PTSD; Trauma

Keywords

Estrogen; Stress Disorder

Outcome Measures

Primary Outcomes (3)

• Change in amygdala response to fearful faces stimuli

  Responses to threat cues will be assessed by fMRI responses as participants view 15 blocks each of fearful face and neutral face stimuli, while amygdala reactivity is measured.

  Mid-cycle second cycle, Mid-cycle third cycle (each cycle is an average of 28 days)

• Change in amygdala response to fear conditioning task

  Indicators of fear conditioning will be assessed by fMRI during the fear conditioning tasks. Deficits in fear inhibition have been present in persons with PTSD and during phases of the ovarian cycle.

  Mid-cycle second cycle, Mid-cycle third cycle (each cycle is an average of 28 days)

• Change in ventromedial prefrontal cortex (vmPFC) activation during the fear extinction task

  Indicators of fear extinction will be assessed by fMRI during the fear extinction tasks. Fear extinction is impaired in persons with PTSD and depends on the vmPFC and its inhibition of amygdala responses to threat stimuli.

  Mid-cycle second cycle, Mid-cycle third cycle (each cycle is an average of 28 days)

Secondary Outcomes (2)

• Change in PTSD checklist for DSM-5 (PCL-5)

  Baseline, Mid-cycle second cycle, Mid-cycle third cycle (each cycle is an average of 28 days)

• Change in Beck Depression Inventory (BDI)

  Baseline, Mid-cycle second cycle, Mid-cycle third cycle (each cycle is an average of 28 days)

Study Arms (12)

Cohort 1: PTSD Receiving Estradiol then Placebo

EXPERIMENTAL

Participants with PTSD will record their first cycle with the Clue app. They will receive the estradiol patch during the second cycle, and the placebo patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 1: PTSD Receiving Placebo then Estradiol

EXPERIMENTAL

Participants with PTSD will record their first cycle with the Clue app. They will receive the placebo patch during the second cycle, and the estradiol patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 1: Trauma without PTSD Receiving Estradiol then Placebo

ACTIVE COMPARATOR

Participants with trauma exposure will record their first cycle with the Clue app. They will receive the estradiol patch during the second cycle, and the placebo patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 1: Trauma without PTSD Receiving Placebo then Estradiol

ACTIVE COMPARATOR

Participants with trauma exposure will record their first cycle with the Clue app. They will receive the placebo patch during the second cycle, and the estradiol patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 1: Healthy Controls Receiving Estradiol then Placebo

ACTIVE COMPARATOR

Participants without trauma history or psychiatric disorder will record their first cycle with the Clue app. They will receive the estradiol patch during the second cycle, and the placebo patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 1: Healthy Controls Receiving Placebo then Estradiol

ACTIVE COMPARATOR

Participants without trauma history or psychiatric disorder will will record their first cycle with the Clue app. They will receive the placebo patch during the second cycle, and the estradiol patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 2: PTSD Receiving Estradiol then Placebo

EXPERIMENTAL

Participants with PTSD will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the estradiol patch before getting the MRI. They will apply the placebo patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 2: PTSD Receiving Placebo then Estradiol

EXPERIMENTAL

Participants with PTSD will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the placebo patch before getting the MRI. They will apply the estradiol patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 2: Trauma Control Receiving Estradiol, then Placebo

ACTIVE COMPARATOR

Participants with trauma exposure will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the estradiol patch before getting the MRI. They will apply the placebo patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 2: Trauma Control Receiving Placebo then Estradiol

ACTIVE COMPARATOR

Participants with trauma exposure will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the placebo patch before getting the MRI. They will apply the estradiol patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 2: Healthy Control Receiving Estradiol then Placebo

ACTIVE COMPARATOR

Participants without trauma history or psychiatric disorder will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the estradiol patch before getting the MRI. They will apply the placebo patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Cohort 2: Healthy Control Receiving Placebo then Estradiol

ACTIVE COMPARATOR

Participants without trauma history or psychiatric disorder will begin daily urine ovulation tests on Day 11 of their first cycle, and will record the results with the Clue app. During the second month of cycle monitoring, the MRI will be scheduled 5-7 days after they record a positive ovulation test (during luteal phase) and they will use the placebo patch before getting the MRI. They will apply the estradiol patch during the third cycle.

Drug: Estradiol patch; Other: Placebo patch

Interventions

Estradiol patch DRUG

Estradiol (E2) patches at a dose of 100ug will be applied 24-48 hours before the MRI scan is performed.

Cohort 1: Healthy Controls Receiving Estradiol then Placebo; Cohort 1: Healthy Controls Receiving Placebo then Estradiol; Cohort 1: PTSD Receiving Estradiol then Placebo; Cohort 1: PTSD Receiving Placebo then Estradiol; Cohort 1: Trauma without PTSD Receiving Estradiol then Placebo; Cohort 1: Trauma without PTSD Receiving Placebo then Estradiol; Cohort 2: Healthy Control Receiving Estradiol then Placebo; Cohort 2: Healthy Control Receiving Placebo then Estradiol; Cohort 2: PTSD Receiving Estradiol then Placebo; Cohort 2: PTSD Receiving Placebo then Estradiol; Cohort 2: Trauma Control Receiving Estradiol, then Placebo; Cohort 2: Trauma Control Receiving Placebo then Estradiol

Placebo patch OTHER

Placebo patch identical to the estradiol patch will be applied 24-48 hours before the MRI scan is performed.

Cohort 1: Healthy Controls Receiving Estradiol then Placebo; Cohort 1: Healthy Controls Receiving Placebo then Estradiol; Cohort 1: PTSD Receiving Estradiol then Placebo; Cohort 1: PTSD Receiving Placebo then Estradiol; Cohort 1: Trauma without PTSD Receiving Estradiol then Placebo; Cohort 1: Trauma without PTSD Receiving Placebo then Estradiol; Cohort 2: Healthy Control Receiving Estradiol then Placebo; Cohort 2: Healthy Control Receiving Placebo then Estradiol; Cohort 2: PTSD Receiving Estradiol then Placebo; Cohort 2: PTSD Receiving Placebo then Estradiol; Cohort 2: Trauma Control Receiving Estradiol, then Placebo; Cohort 2: Trauma Control Receiving Placebo then Estradiol

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• African American women
• A menstrual period within the past 60 days
• Able and willing to give informed consent
• Must have a smart phone and willing to install the Clue app

You may not qualify if:

• Women currently taking any form of hormone-based birth control or other hormonal supplement
• Women who are pregnant or breastfeeding
• Current psychoactive medication use
• Nicotine use or smoking
• Hypercoagulable conditions
• History of embolism
• Current symptoms of psychosis or bipolar disorder
• History of major head injury or neurological disorder
• Weight \>250lbs (a maximum weight to allow for participants to fit comfortably inside the bore of the MRI machine) and typical physical contraindications for MRI such as metal implants

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Wounds and Injuries; Stress Disorders, Traumatic

Interventions

Ortho Evra

Condition Hierarchy (Ancestors)

Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Jennifer Stevens, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization will be double blind, with the key held by the study coordinator in a locked file. The study coordinator will do checks of appropriate enrollment to groups after each 20 participants, but no blind will be broken to individuals analyzing study data. Grady pharmacy services will also hold the randomization schedule, as they will dispense the appropriate patch at the appropriate time point.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Women will participate in one cycle with the estrogen patch and one cycle with the placebo patch. Each cohort will include 40 participants in each of the three study arms for a total of 240 participants.

Study Record Dates

• First Submitted: May 30, 2019
• First Posted: June 4, 2019
• Study Start: November 11, 2019
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be uploaded to the database every 6 months following the standard NIH schedule (Jan 15 and July 15 of each year of funding). Data will be released publicly within 4 months after submission.
• Access Criteria: Data access requests will be submitted to RDoC database, and approved by NIH before data are shared. Only research investigators sponsored by an NIH recognized institution with federal wide assurance will receive access. Any analysis approved by NIH. Web-based access to the RDoC data archive.

Locations

US (1)