Suicidal IdeationPhase 4CLEAR-2NCT03498313
Unique Effects of Perimenstrual Estradiol or Progesterone Supplementation on Perimenstrual Suicidality
A Phase 4 study of Suicidal Ideation, run by University of Illinois at Chicago at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Suicidal Ideation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jul 2018to 9 May 2021
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois Neuropsychiatric Institute
Chicago, Illinois, 60612
About this study
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.
Read the 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 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.
- Conditions
- Suicidal Ideation
- Being tested
- Transdermal Estradiol + Placebo, Oral Micronized Progesterone + Placebo, Placebos
- Keywords
- steroid hormones, estradiol, estrogen, progesterone, depression, suicide
- Medical subject headings
- Suicidal Ideation, Depression, Suicide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transdermal Estradiol + PlaceboDrug
Also called Climara, sugar pill
.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 + PlaceboDrug
Also called Prometrium, placebo patch
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.
PlacebosDrug
Also called sugar pill, placebo patch
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Days 1 to 17 following positive LH test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study start27 Jul 2018
- Primary completion9 May 2021
- Study completion9 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Suicidal IdeationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Crossover 3-condition placebo-controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois at Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Tory Anne Eisenlohr-Moul, University of Illinois at Chicago
- Investigators
- Tory A Eisenlohr-Moul, PhD, Principal investigator, University of Illinois at Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03498313
- Sponsor's protocol ID
- 2018-0189
- Other IDs
- R00MH109667
- Acronym
- CLEAR-2
- Status last verified
- Aug 2022
- First submitted
- 6 Apr 2018
- Last updated
- 14 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Law KC, O'Connell KL, Barone JC, Eisenlohr-Moul TA. Examining Suicidal Ideation and Capability Across the Menstrual Cycle. Suicide Life Threat Behav. 2026 Apr;56(2):e70084. doi: 10.1111/sltb.70084.
PubMed 41913970