Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality

Suicidal Ideation Clinical Trial

Official title:

Ovarian Hormone Withdrawal and Suicide Risk: An Experimental Approach

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03720847
• Other study ID #: 16-2078
• Secondary ID: K99MH109667
• Status: Completed
• Phase: Phase 4
• Start date: December 31, 2016
• Est. completion date: November 2017

Study information

• Verified date: October 2018
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

A large number of observational studies have documented increased risk of suicide attempt, suicide death, and more lethal attempts during the perimenstrual (around menses) window of the female reproductive cycle; however, no experiments have investigated the causal role of ovarian steroid changes across the natural perimenstrual period in risk factors for acute suicidality. In response, the proposed experimental work investigates a causal role of perimenstrual withdrawal from the hormones estradiol (E2) and progesterone (P4) in previously-documented acute perimenstrual increases in suicidality.

Participants are 30 women between the ages of 18 and 45 with current suicidal ideation but minimal risk for suicide attempt. Using a placebo-controlled, crossover within-person design, the experiment tests the hypothesis that suicidality will be heightened during natural perimenstrual E2/P4 withdrawal (under placebo), but that experimental prevention of this perimenstrual E2/P4 withdrawal (with exogenous administration of E2/P4 hormones) will prevent these perimenstrual increases in suicidality and associated risk factors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2017
• Est. primary completion date: November 2017
• 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 18-29)

• 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.

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, 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 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.

Related Conditions & MeSH terms

• Suicidal Ideation

Intervention

Drug:
• Estradiol Transdermal Patch 0.1 mg/24 hrs
Estradiol transdermal patch delivering 0.1 mg/24 hour administered by affixing to skin for 14 days starting on day 7 after ovulation
• Oral Micronized Progesterone
100 mg oral micronized progesterone taken orally twice daily for 14 days starting day 7 after ovulation
• Inactive Clear Patch
Matching placebo patch administered by affixing to skin for 14 days starting on day 7 after ovulation
• Placebo capsule
Matching placebo capsules administered twice daily for 14 days starting day 7 after ovulation

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Perimenstrual Change in Beck Hopelessness Scale (BHS) Score	Hopelessness is assessed with the Beck Hopelessness Scale, a 20-item self-report measure with true-false items that assess hopelessness and the extent of positive and negative beliefs about the future. This measure will be collected at the second lab visit in each condition (day 7 following ovulation). Summed scores range from 0 to 20. Scores provide a measure of the severity of self-reported hopelessness: 0-3 minimal, 4-8 mild, 9-14 moderate, and 15-20 severe. Higher values on the raw scale represent greater hopelessness. Perimenstrual change scores are calculated for each person in a given condition as the person's score at lab 2 (in the perimenstrual phase) minus the person's score at lab 1 (midluteal phase). Therefore, positive values represent degree of perimenstrual increase in symptoms, and negative values represent degree of perimenstrual decrease.	Day 7 of Each Condition (Lab 2)
Secondary	Perimenstrual Change in Center for Epidemiological Studies Depression Scale (CES-D) Score	The Center for Epidemiological Studies Depression scale (CES-D) includes 20 items that ask the person assessed to report his or her experience of mood symptoms. Instructions were modified such that symptoms were rated over the past week (rather than the standard 2 weeks). This measure will be collected at the second lab visit in each condition (day 7 following ovulation). Scores can range from zero to 60, with most persons attaining a score of 15 or less. Higher scores are considered worse. Perimenstrual change scores are calculated for each person in a given condition as the person's score at lab 2 (in the perimenstrual phase) minus the person's score at lab 1 (midluteal phase). Therefore, positive values represent degree of perimenstrual increase in symptoms, and negative values represent degree of perimenstrual decrease.	Day 7 of Each Condition (Lab 2)
Secondary	Perimenstrual Change in Lack of Premeditation Subscale Score of the "Urgency, Premeditation, Perseverance, Sensation Seeking, and Positive Urgency (UPPSP) Impulsivity Scale"	The UPPS-P (Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency Impulsivity Scale) Lack of Premeditation subscale includes 11 items that ask the person to report experience of impulsivity over the past two weeks. Instructions were modified such that symptoms were rated over the past week (rather than the standard 2 weeks). This measure will be collected at the second lab visit in each condition (day 7 following ovulation). Scores can range from 11 to 44. Higher scores are considered worse. Perimenstrual change scores are calculated for each person in a given condition as the person's score at lab 2 (in the perimenstrual phase) minus the person's score at lab 1 (midluteal phase). Therefore, positive values represent degree of perimenstrual increase in symptoms, and negative values represent degree of perimenstrual decrease.	Day 7 of Each Condition (Lab 2)
Secondary	Perimenstrual Changes in Patient-Reported Outcomes Measurement Information Systems (PROMIS) Anxiety Scale Score	The PROMIS (Patient-Reported Outcomes Measurement Information Systems) Anxiety scale includes 7 items that ask the person assessed to report his or her experience of anxiety over the past two weeks. Instructions were modified such that symptoms were rated over the past week (rather than the standard 2 weeks). This measure will be collected at the second lab visit in each condition (day 7 following ovulation). Scores can range from 7 to 35. Higher scores are considered worse. Perimenstrual change scores are calculated for each person in a given condition as the person's score at lab 2 (in the perimenstrual phase) minus the person's score at lab 1 (midluteal phase). Therefore, positive values represent degree of perimenstrual increase in symptoms, and negative values represent degree of perimenstrual decrease.	Day 7 of Each Condition (Lab 2)
Secondary	Perimenstrual Change in State Self-Esteem Scale Social Evaluation Subscale (SSES-SE) Score	The SSES-SE (State Self-Esteem Scale Social Evaluation subscale) includes 7 items that ask the person assessed to report his or her experience of social self-esteem--that is, a sense that others are evaluating one in a positive light-- in the present moment. Instructions were modified such that symptoms were rated over the past week (rather than the standard 2 weeks). This measure will be collected at the second lab visit in each condition (day 7 following ovulation). Scores can range from 7 to 49. Higher scores are considered better as they indicate better social self-esteem. Perimenstrual change scores are calculated for each person in a given condition as the person's score at lab 2 (in the perimenstrual phase) minus the person's score at lab 1 (midluteal phase). Therefore, positive values represent degree of perimenstrual increase in self-esteem, and negative values represent degree of perimenstrual decrease.	Day 7 of Each Condition (Lab 2)