NCT06191289

Neurocognitive Mechanisms of Perimenstrual Estrogen Effects on Suicidality

Clarifying the Endocrinology of Acute Risk 4 (CLEAR-4): Neurocognitive Mechanisms of Perimenstrual Estrogen Effects on Suicidality

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: University of Illinois at Chicago · Academic / Other
• Sex: Female
• Age: 20 Years – 40 Years
• Healthy volunteers: Not accepted

Summary

This within-person, crossover, 2-condition, placebo-controlled study compares the impact of two perimenstrual conditions on severity of suicidal symptoms in females with past-month suicidality but minimal risk of imminent suicide attempt. The two conditions are (1) perimenstrual administration of estradiol and (2) natural perimenstrual withdrawal from estradiol during placebo.

Detailed description

Previous work from our group demonstrates that perimenstrual worsening of suicidal thoughts in females is caused by normal perimenstrual withdrawal from the ovarian steroid estradiol (E2), since perimenstrual administration of E2+P4 or E2 alone prevented the perimenstrual worsening of suicidal ideation observed under placebo. In the present study, we follow up on that work with an additional mechanistic crossover trial in which E2 will be administered perimenstrually (E2 condition) or not (PBO condition) and neurocognitive mechanisms of suicidal symptom improvement will be probed. 50 (30 completers) female outpatients, with past-month suicidal ideation but minimal imminent risk for attempt, will complete self-reports and clinical interviews measuring the presence and severity of suicidal ideation in each of two conditions (A, B: order randomized across two menstrual cycles): (A) perimenstrual E2 withdrawal/depletion (under placebo), (B) perimenstrual administration of E2. A washout cycle will separate conditions. Analyses will compare the perimenstrual trajectories of symptoms and suicidality across the two conditions.

Conditions

• Suicide

Interventions

Type	Name	Description
DRUG	Transdermal Estradiol	1mg/24hr transdermal estradiol for 14 days starting day 7 after positive urine luteinizing hormone test Other Names: Climara
OTHER	Placebo	Weekly application of a placebo patch for 14 days starting day 7 after positive urine luteinizing hormone test

Timeline

• Start date: 2024-03-16
• Primary completion: 2024-12-01
• Completion: 2024-12-01
• First posted: 2024-01-05
• Last updated: 2025-10-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study