Unique Effects of Perimenstrual Estradiol or Progesterone Supplementation on Perimenstrual Suicidality

NCT03498313 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 2018-0189R00MH109667
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Suicidal Ideation

Keywords

steroid hormones; estradiol; estrogen; progesterone; depression; suicide

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Transdermal Estradiol + Placebo

EXPERIMENTAL

.1mg per 24 hours transdermal estradiol applied to the skin weekly, and sugar pill manufactured to mimic the progesterone pills taken twice daily by mouth, for 14 days.

Drug: Transdermal Estradiol + Placebo

Oral Micronized Progesterone + Placebo

EXPERIMENTAL

100 mg oral micronized progesterone pill taken twice daily by mouth, and clear patch manufactured to mimic the E2 patch applied to the skin weekly, for 14 days.

Drug: Oral Micronized Progesterone + Placebo

Placebos

PLACEBO COMPARATOR

Sugar pill designed to mimic the P4 pills taken twice daily by mouth, and clear patch manufactured to mimic the E2 patch applied to the skin weekly, for 14 days.

Drug: Placebos

Interventions

Transdermal Estradiol + Placebo DRUG

.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.

Also known as: Climara, sugar pill

Transdermal Estradiol + Placebo

Oral Micronized Progesterone + Placebo DRUG

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.

Also known as: Prometrium, placebo patch

Oral Micronized Progesterone + Placebo

Placebos DRUG

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.

Also known as: sugar pill, placebo patch

Placebos

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• 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 18.00-29.99)
• 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.

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 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.
• 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.

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Illinois Neuropsychiatric Institute

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Suicidal Ideation; Depression; Suicide

Interventions

Estradiol; Sugars; Progesterone

Condition Hierarchy (Ancestors)

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; Carbohydrates; Pregnenediones; Pregnenes; Pregnanes; Corpus Luteum Hormones; Progesterone Congeners

Results Point of Contact

• Title: Dr. Tory Eisenlohr-Moul, Assistant Professor of Psychiatry
• Organization: University of Illinois at Chicago

temo@uic.edu

859-317-0503

Study Officials

• Tory A Eisenlohr-Moul, PhD

  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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Crossover 3-condition placebo-controlled trial

Study Record Dates

• First Submitted: April 6, 2018
• First Posted: April 13, 2018
• Study Start: July 27, 2018
• Primary Completion: May 9, 2021
• Study Completion: May 9, 2021
• Last Updated: September 14, 2022
• Results First Posted: September 14, 2022

Record last verified: 2022-08

Locations

US (1)