Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality

NCT03720847 | Completed Phase 4 Results DMC

• 2 other identifiers: 16-2078K99MH109667
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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) natural perimenstrual withdrawal from estradiol and progesterone (during placebo), (2) perimenstrual stabilization of estradiol and progesterone using transdermal estradiol and oral micronized progesterone.

Conditions

Suicidal Ideation

Keywords

Steroid hormones; Estradiol; Progesterone; Depression; Suicide

Outcome Measures

Primary Outcomes (2)

• Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Ideation Score

  The SITBI is an interview designed to assess various aspects of suicidality, including ideation, planning, intent, and behavior. This outcome is a single item representing suicidal ideation severity from the SITBI interview which was measured as part of a daily questionnaire completed via smart phone. The question was: "Today, how intense were your thoughts of killing yourself?". Each day, individuals chose a response ranging from 0 (Not at All) to 4 (Severe). Values could range from 0 to 4, and higher values indicate more suicidal ideation. Perimenstrual change scores are calculated for each person in a given condition as the mean of scores in the perimenstrual phase (final seven days of medication use in that condition) minus the mean in the midluteal phase (7 days starting on the day of the positive ovulation test for that condition). Therefore, positive values represent a perimenstrual increase in symptoms, and negative values represent a perimenstrual decrease in symptoms.

  Midluteal Baseline and Perimenstrual

• Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Planning Score

  The SITBI is an interview designed to assess various aspects of suicidality. This outcome is a single item representing suicidal planning from the SITBI interview was measured as part of a daily questionnaire via smart phone. The question was: "Today, how seriously did you consider acting on a suicide plan?". Each day, individuals chose a response from 0 (Not at All) to 4 (Severe). Values could range from 0 to 4, and higher values indicate more suicidal planning. Perimenstrual change scores are calculated for each person in a given condition as the mean of scores in the perimenstrual phase (final seven days of medication use in that condition) minus the mean in the midluteal phase (7 days starting on the day of the positive ovulation test for that condition). Therefore, positive values represent a perimenstrual increase in symptoms, and negative values represent a perimenstrual decrease.

  Midluteal Baseline and Perimenstrual

Secondary Outcomes (5)

• Perimenstrual Change in Beck Hopelessness Scale (BHS) Score

  Day 7 of Each Condition (Lab 2)

• Perimenstrual Change in Center for Epidemiological Studies Depression Scale (CES-D) Score

  Day 7 of Each Condition (Lab 2)

• Perimenstrual Change in Lack of Premeditation Subscale Score of the "Urgency, Premeditation, Perseverance, Sensation Seeking, and Positive Urgency (UPPSP) Impulsivity Scale"

  Day 7 of Each Condition (Lab 2)

• Perimenstrual Changes in Patient-Reported Outcomes Measurement Information Systems (PROMIS) Anxiety Scale Score

  Day 7 of Each Condition (Lab 2)

• Perimenstrual Change in State Self-Esteem Scale Social Evaluation Subscale (SSES-SE) Score

  Day 7 of Each Condition (Lab 2)

Study Arms (2)

Active condition, then Inactive condition

EXPERIMENTAL

Beginning 7 days after ovulation, active treatment begins 7 days after ovulation with an estradiol transdermal patch (0.1 mg/24 hrs) applied to the skin weekly (spanning 14 days of treatment) along with (active) 100 mg oral micronized progesterone capsules taken twice daily by mouth for 14 days. A 1-month washout is observed. Then, beginning 7 days after ovulation, inactive placebo capsules will be taken twice daily by mouth along with the application of inactive clear patches applied to the skin weekly for 14 days.

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

Inactive condition, then active condition

PLACEBO COMPARATOR

Beginning 7 days after ovulation, inactive placebo capsules will be taken twice daily by mouth along with the application of inactive clear patches applied to the skin weekly for 14 days. After completing a 1-month washout, active treatment begins 7 days after ovulation with an (active) estradiol transdermal patch applied to the skin weekly (spanning 14 days of treatment) along with (active) 100 mg oral micronized progesterone capsules taken twice daily by mouth for 14 days.

Drug: Estradiol Transdermal Patch 0.1 mg/24 hrs; Drug: Oral Micronized Progesterone; 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

Active condition, then Inactive condition; Inactive condition, then active condition

Oral Micronized Progesterone DRUG

100 mg oral micronized progesterone taken orally twice daily for 14 days starting day 7 after ovulation

Also known as: Prometrium

Active condition, then Inactive condition; Inactive condition, then active condition

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

Active condition, then Inactive condition; Inactive condition, then active condition

Placebo capsule DRUG

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

Also known as: Sugar pill

Active condition, then Inactive condition; Inactive condition, then active condition

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 North Carolina, Chapel Hill: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 60657, United States

Location

Related Publications (3)

• Barone JC, Wenzel E, Alluri V, Moriarity D, Pinna G, Walsh E, Rubinow DR, Morrow AL, Eisenlohr-Moul TA. Effects of estrogen and progesterone on neuroactive steroids and cytokines in patients with suicidality. Psychoneuroendocrinology. 2023 Nov;157:106359. doi: 10.1016/j.psyneuen.2023.106359. Epub 2023 Aug 9.

  PMID: 37611527 DERIVED

• Owens SA, Schmalenberger KM, Bowers S, Rubinow DR, Prinstein MJ, Girdler SS, Eisenlohr-Moul TA. Cyclical exacerbation of suicidal ideation in female outpatients: Prospective evidence from daily ratings in a transdiagnostic sample. J Psychopathol Clin Sci. 2023 Aug;132(6):704-715. doi: 10.1037/abn0000838. Epub 2023 Jun 15.

  PMID: 37326562 DERIVED

• Eisenlohr-Moul TA, Bowers SM, Prinstein MJ, Schmalenberger KM, Walsh EC, Young SL, Rubinow DR, Girdler SS. Effects of acute estradiol and progesterone on perimenstrual exacerbation of suicidal ideation and related symptoms: a crossover randomized controlled trial. Transl Psychiatry. 2022 Dec 30;12(1):528. doi: 10.1038/s41398-022-02294-1.

  PMID: 36585408 DERIVED

MeSH Terms

Conditions

Suicidal Ideation; Depression; Suicide

Interventions

Estradiol; Progesterone; Sugars

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

Results Point of Contact

• Title: Tory Eisenlohr-Moul
• Organization: University of North Carolina at Chapel Hill

moul@med.unc.edu

859-317-0503

Study Officials

• Tory A Eisenlohr-Moul, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Susan Girdler, PhD

  University of North Carolina, Chapel Hill

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

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 UNC investigational drug service.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Crossover 2-Condition Placebo-Controlled Trial

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: October 25, 2018
• Study Start: December 31, 2016
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: February 4, 2019
• Results First Posted: February 4, 2019

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: 9 to 36 months following publication
• Access Criteria: Following execution of a data use/sharing agreement with the University of North Carolina at Chapel Hill

Locations

US (1)