Cyclical Neuroactive Steroid Changes, Arousal, and Proximal Suicide Risk: An Experimental Approach

NCT04112368 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 2019-0624
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

Female suicide attempts occur more often in the weeks before and after menses onset, and have been linked to ovarian hormone withdrawal. The proposed project will use a two-week intervention to stabilize hormones in females with recent suicidal thoughts; this paradigm is a safe way to learn how cyclical changes in hormones and their metabolites influence short-term risk of suicide. The data acquired will contribute to our understanding of the biology of acute suicide risk and advance efforts to develop safe and effective treatments that eliminate predictable monthly worsening of suicide risk in reproductive-age females.

Conditions

Suicidal Ideation

Outcome Measures

Primary Outcomes (2)

• Perimenstrual Change in Daily Adult Suicidal Ideation Questionnaire (ASIQ) Scores

  The Adult Suicidal Ideation Questionnaire (ASIQ) is a 25-item self-report questionnaire assessing suicidality. Each day, individuals rate each of 25 items on a scale from 1 (Not at All) to 6 (Extreme). Mean scores are computed, providing a single number for each day that represents the participant's mean suicidal ideation (1 to 6), with higher daily values representing more severe suicidal ideation. Perimenstrual change scores are calculated for each person in each condition as the mean of scores in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean in the midluteal phase (days +0 to +5). Therefore, positive values represent a perimenstrual increase in suicidal ideation, and negative values represent a perimenstrual decrease.

  Mean daily rating in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean daily rating in the midluteal phase (days +0 to +5)

• Perimenstrual Change in Daily Columbia Suicide Severity Rating Scale (C-SSRS) Screening Interview Planning Item Scores

  The Columbia Suicide Severity Rating Scale is an interview designed to assess various aspects of suicide risk. In the present study, this questionnaire is administered daily via phone interview as part of a risk screening process. Here, we utilize a single dichotomous outcome from a single item representing suicidal planning from the C-SSRS interview: "Today, have you thought about how or when you might kill yourself?". Each day, individuals chose either "Yes" (coded as 1) or "No" (coded as 0). Perimenstrual change scores are calculated for each person in each condition as the mean of scores in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean in the midluteal phase (days +0 to +5). Therefore, positive values represent a perimenstrual increase in suicidal planning, and negative values represent a perimenstrual decrease.

  Mean daily rating in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean daily rating in the midluteal phase (days +0 to +5)

Secondary Outcomes (2)

• Perimenstrual Change in Daily Beck Hopelessness Scale (BHS) Short Form Scores

  Mean daily rating in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean daily rating in the midluteal phase (days +0 to +5)

• Perimenstrual Change in Daily Brief Agitation Measure (BAM) Scores

  Mean daily rating in the perimenstrual phase (days +12 to +17 following a positive luteinizing hormone surge in urine on day=0) minus the mean daily rating in the midluteal phase (days +0 to +5)

Study Arms (2)

Transdermal Estradiol + Oral Micronized Progesterone

EXPERIMENTAL

0.1 mg/24hr transdermal estradiol patch applied weekly and 100 mg oral micronized progesterone taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.

Drug: Estradiol Transdermal Patch 0.1 mg/24 hrs; Drug: Oral Micronized Progesterone 200mg; Drug: Inactive Clear Patch; Drug: Placebo capsule

Placebo Patch + Placebo Pills

EXPERIMENTAL

Placebo patch (selected to match transdermal estradiol patch) applied weekly and placebo pills (blinded to match oral micronized progesterone) taken twice daily by mouth, for 14 days starting 7 days after a positive urine luteinizing hormone (LH) test.

Drug: Estradiol Transdermal Patch 0.1 mg/24 hrs; Drug: Oral Micronized Progesterone 200mg; Drug: Inactive Clear Patch; Drug: Placebo capsule

Interventions

Estradiol Transdermal Patch 0.1 mg/24 hrs DRUG

Estradiol transdermal patch delivering 0.1 mg/24 hour administered by affixing to skin for 14 days starting on day 7 after ovulation

Also known as: Climara

Placebo Patch + Placebo Pills; Transdermal Estradiol + Oral Micronized Progesterone

Oral Micronized Progesterone 200mg DRUG

100 mg oral micronized progesterone taken orally twice daily for 14 days starting day 7 after ovulation (200mg total per day)

Also known as: Prometrium

Placebo Patch + Placebo Pills; Transdermal Estradiol + Oral Micronized Progesterone

Inactive Clear Patch DRUG

Matching placebo patch administered by affixing to skin for 14 days starting on day 7 after ovulation

Also known as: Placebo transdermal patch

Placebo Patch + Placebo Pills; Transdermal Estradiol + Oral Micronized Progesterone

Placebo capsule DRUG

Matching placebo capsules administered twice daily for 14 days starting day 7 after ovulation

Also known as: Sugar pill

Placebo Patch + Placebo Pills; Transdermal Estradiol + Oral Micronized Progesterone

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Since the study is focused on the menstrual cycle, the study includes only those assigned female sex at birth
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to adhere to medication regimen
• Speaks English
• Assigned female at birth with intact ovaries
• Premenopausal
• Normal menstrual cycles between 25-35 days
• Under current care of an outpatient mental health provider with visits occurring at least once every 3 months.
• At least 1 year postpartum.
• Willing to use a barrier method of birth control during the study.
• Normal weight (BMI between 18-29)
• Must report at least some recent suicidal ideation (in the past month) at the time of recruitment.
• Must be categorized as having acceptably low imminent risk for suicidal crisis/attempt by a licensed clinical psychologist utilizing evidence-based clinical and research guidelines for imminent suicide risk management.

You may not qualify if:

• Must not be pregnant, breastfeeding, or trying to become pregnant.
• Must not be taking any form of exogenous hormones or hormonal intrauterine device, and must have ended previous use of hormonal preparations at least one month prior to the study.
• Must not have a personal history of any chronic medical condition, including but not limited to metabolic or autoimmune disease, epilepsy, endometriosis, cancer, diabetes, cardiovascular, gastrointestinal, hepatic, renal, or pulmonary disease, and no personal or first degree family history of thromboembolic events.
• Must not report a history of clinical diagnosis or treatment for postpartum depression or premenstrual dysphoric disorder (Note: Premenstrual Dysphoric - - - Disorder diagnosis must have been made based on prospective daily ratings).
• Must not report any history of manic episode, any history of psychotic symptoms, or current substance use disorder.

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois Neuropsychiatric Institute

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Suicidal Ideation

Interventions

Estradiol; Progesterone; Sugars

Condition Hierarchy (Ancestors)

Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnenediones; Pregnenes; Pregnanes; Corpus Luteum Hormones; Progesterone Congeners; Carbohydrates

Results Point of Contact

• Title: Tory Eisenlohr-Moul
• Organization: University of Illinois Chicago

temo@uic.edu

859-317-0503

Study Officials

• Tory A Eisenlohr-Moul, Ph.D

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical placebos provided by the University of Illinois at Chicago investigational drug service.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Crossover 2-Condition Placebo-Controlled Trial

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: October 2, 2019
• Study Start: September 15, 2020
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: December 19, 2025
• Results First Posted: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)