Neuroendocrine Risk for PTSD in Women

Emory University

Status and phase: Completed; Early Phase 1

Conditions: PTSD; Trauma

Treatments: Drug: Estradiol patch; Other: Placebo patch

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03973229

IRB00103595

1R01MH117009-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Women will be recruited through Grady Trauma Project (GTP), a large longstanding study of civilian trauma and PTSD conducted at Grady Memorial Hospital in Atlanta, Georgia.

Full description

The majority of Americans will experience a traumatic event during their lifetimes. However, women are twice as likely as men to experience negative psychiatric outcomes following trauma, including post-traumatic stress disorder (PTSD) and depression. The reason for the increased prevalence in women is unclear, partially because of the historical lack of investigation of females in both human and pre-clinical animal research. The researchers propose to investigate the role of sex hormones in contributing to women's risk for PTSD. The study will investigate relationships between trauma exposure and women's menstrual cycle, examining key events in the cycle, including menstruation, ovulation, and mood changes. The study will then examine relationships between the level of naturally-cycling estradiol (E2; the primary female sex hormone), and brain-based measures of stress vulnerability. This includes amygdala hyper-reactivity to threat.

The trial will study if trauma-exposed women with lower E2 levels during the luteal phase will report greater PTSD symptoms, and show more stress-vulnerable patterns of brain function. It will also examine the effects of exogenous application of estrogen on PTSD symptoms.

Women will begin tracking their cycle using a free and widely-used cycle-tracking smartphone app "Clue" for one full menstrual cycle.

• For Study Aims 1 & 2 (N=120): Participants will be contacted on the first day of their menstrual period in the second cycle, and scheduled for an MRI with a 4-day window (early follicular phase). Participants will be randomized to begin with either the E2 or placebo patch. The will receive an E2 or placebo patch 1 day prior to the MRI visit, with a blood draw on the morning of the MRI visit (to assess hormone levels), 1 hour prior to scanning. On the first day of the third cycle (onset of menses), women will all be scheduled for their second MRI visit. Participants will experience the opposite condition from their first MRI scan. They will receive an E2 or placebo patch 1 day prior to the MRI visit in the afternoon, with a blood draw on the morning of the MRI visit, 1 hour prior to scanning.
• For Study Aim 3 (N=120): Participants will begin daily urine ovulation tests on Day 11 of their cycle, and will record the results in Clue. When participants record a positive ovulation test during the second month of cycle monitoring, they will be contacted to schedule their MRI visit 5-7 days following ovulation (during the luteal phase). The experimental protocol will otherwise be the same as in Aims 1 and 2, with participants randomized to either E2 or placebo at the first visit and returning the next month for the other condition.

The scientific premise of this study is that low E2 may contribute to stress vulnerability in women. Findings may aid in the development of treatments that will enhance women's mental health outcomes following trauma.

Enrollment: 250 patients

Sex: Female

Ages: 18 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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250 participants in 12 patient groups

Cohort 1: PTSD Receiving Estradiol then Placebo

Experimental group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 1: PTSD Receiving Placebo then Estradiol

Experimental group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 1: Trauma without PTSD Receiving Estradiol then Placebo

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 1: Trauma without PTSD Receiving Placebo then Estradiol

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 1: Healthy Controls Receiving Estradiol then Placebo

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 1: Healthy Controls Receiving Placebo then Estradiol

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 2: PTSD Receiving Estradiol then Placebo

Experimental group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 2: PTSD Receiving Placebo then Estradiol

Experimental group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 2: Trauma Control Receiving Estradiol, then Placebo

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 2: Trauma Control Receiving Placebo then Estradiol

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 2: Healthy Control Receiving Estradiol then Placebo

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch

Cohort 2: Healthy Control Receiving Placebo then Estradiol

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Estradiol patch