Unique Effects of Perimenstrual Estradiol or Progesterone Supplementation on Perimenstrual Suicidality

Suicidal Ideation Clinical Trial

— CLEAR-2  

Official title:

Unique Effects of Perimenstrual Estradiol or Progesterone Supplementation on Perimenstrual Suicidality

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03498313
• Other study ID #: 2018-0189
• Secondary ID: R00MH109667
• Status: Completed
• Phase: Phase 4
• Start date: July 27, 2018
• Est. completion date: May 9, 2021

Study information

• Verified date: August 2022
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This within-person, crossover, 3-condition, placebo-controlled study compares the impact of three perimenstrual conditions on severity of suicidal symptoms in females with past-month suicidality but minimal risk of imminent suicide attempt. The three conditions are (1) perimenstrual withdrawal from estradiol only (during progesterone stabilization), (2) perimenstrual withdrawal from progesterone only (during estradiol stabilization), and (3) perimenstrual withdrawal from both estradiol and progesterone during placebo.

Description:

Previous work from our group demonstrates that perimenstrual worsening of suicidal thoughts in females is caused by normal perimenstrual withdrawal from the ovarian steroids estradiol (E2) and progesterone (P4), since perimenstrual stabilization of E2+P4 prevented the perimenstrual worsening of suicidal ideation observed under placebo. In the present study, we follow up on that work with an additional mechanistic trial in which E2 and P4 will be stabilized in separate arms of the study.

60 (30 completers) female outpatients, with past-month suicidal ideation but minimal imminent risk for attempt, will complete self-reports and clinical interviews measuring presence and severity of suicidal ideation in each of three conditions (A, B, C: order randomized across three menstrual cycles): (A) perimenstrual E2/P4 withdrawal (under placebo), (B) perimenstrual P4 withdrawal (exogenous stabilization of E2 only), and (C) perimenstrual E2 withdrawal (exogenous stabilization of P4 only). A washout cycle will separate conditions. Analyses will compare the perimenstrual trajectories of symptoms and suicidality across the three conditions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 9, 2021
• Est. primary completion date: May 9, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 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 18.00-29.99)

• 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.

Exclusion Criteria:

• 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 that may interfere with the aims of the study or make the experimental protocol unsafe, 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.

• Any current cigarette smoking is exclusionary.

• Must not report a current diagnosis of major depressive episode with peripartum onset (current episode), and must not be currently receiving treatment for 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.

• Must not test positive for (unprescribed) opioid use, methamphetamine use, or cocaine use at the start of an experimental condition.

Related Conditions & MeSH terms

• Suicidal Ideation

Intervention

Drug:
• Transdermal Estradiol + Placebo
.1mg/24hr transdermal estradiol for 14 days starting day 7 after positive urine luteinizing hormone test, plus twice daily placebo pills during the same time frame.
• Oral Micronized Progesterone + Placebo
100mg oral micronized progesterone twice daily for 14 days starting day 7 after positive urine luteinizing hormone test, plus weekly application of a placebo patch during the same time frame.
• Placebos
Twice daily placebo pills for 14 days starting day 7 after positive urine luteinizing hormone test, plus weekly application of a placebo patch during the same time frame.

Locations

Country	Name	City	State
United States	University of Illinois Neuropsychiatric Institute	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University of Illinois at Chicago	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cyclical Change in Suicidal Ideation (SI) Severity	Each day, participants completed five items from the Adult Suicidal Ideation Questionnaire (ASIQ; items 1,2,9,17,19). Response options ranged from 1 (no suicidal ideation) to 6 (extreme severity of suicidal ideation). For each participant on each day, "mean daily SI" was calculated as the mean of these five items.; Our outcome, Cyclical Change in SI Severity, is calculated for each person, in each condition, as the DIFFERENCE between mean daily SI during the low-risk early luteal phase days (days LH surge +1,2,3,4,5,6,7) and the high-risk perimenstrual phase days (days LH surge +11,12,13,14,15,16,17), with the subtraction carried out as Perimenstrual mean minus Early Luteal mean. Therefore, this single value represents the degree to which an individual showed perimenstrual worsening of SI within a condition.	Days 1 to 17 following positive LH test