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Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality

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ClinicalTrials.gov Identifier: NCT03720847
Recruitment Status : Completed
First Posted : October 25, 2018
Results First Posted : February 4, 2019
Last Update Posted : February 4, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Tracking Information
First Submitted Date  ICMJE October 24, 2018
First Posted Date  ICMJE October 25, 2018
Results First Submitted Date  ICMJE November 15, 2018
Results First Posted Date  ICMJE February 4, 2019
Last Update Posted Date February 4, 2019
Actual Study Start Date  ICMJE December 31, 2016
Actual Primary Completion Date November 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2019)
  • Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Ideation Score [ Time Frame: Midluteal Baseline and Perimenstrual ]
    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.
  • Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Planning Score [ Time Frame: Midluteal Baseline and Perimenstrual ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
  • Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Ideation [ Time Frame: final seven days of each condition ]
    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). A mean response value across the time frame represents the outcome. Mean values could range from 0 to 4, and higher values indicate more severe suicidal ideation.
  • Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Planning [ Time Frame: final seven days of each condition ]
    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 planning from the SITBI interview was measured as part of a daily questionnaire completed via smart phone. The question was: "Today, how seriously did you consider acting on a suicide plan?". Each day, individuals chose a response ranging from 0 (Not at All) to 4 (Severe). A mean response value across the time frame represents the outcome. Mean values could range from 0 to 4, and higher values indicate greater suicidal planning.
Change History Complete list of historical versions of study NCT03720847 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2019)
  • Perimenstrual Change in Beck Hopelessness Scale (BHS) Score [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    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.
  • Perimenstrual Change in Center for Epidemiological Studies Depression Scale (CES-D) Score [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    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.
  • Perimenstrual Change in Lack of Premeditation Subscale Score of the "Urgency, Premeditation, Perseverance, Sensation Seeking, and Positive Urgency (UPPSP) Impulsivity Scale" [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    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.
  • Perimenstrual Changes in Patient-Reported Outcomes Measurement Information Systems (PROMIS) Anxiety Scale Score [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    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.
  • Perimenstrual Change in State Self-Esteem Scale Social Evaluation Subscale (SSES-SE) Score [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
  • Beck Hopelessness Scale (BHS) [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    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 represent greater hopelessness.
  • Center for Epidemiological Studies Depression Scale (CES-D) [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    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. We modified the instructions 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 as they indicate more frequent or more severe mood symptoms.
  • Urgency, Premeditation, Perseverance, Sensation Seeking, and Positive Urgency (UPPSP) Impulsivity Scale - Lack of Premeditation subscale [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    The UPPS-P (Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency Impulsivity Scale) Lack of Premeditation subscale includes 11 items that ask the person assessed to report his or her experience of impulsivity--particularly impulsivity related to a lack of planing or forethought-- over the past two weeks. We modified the instructions such that symptoms were rated over the past week. 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 as they indicate more frequent or more severe impulsivity symptoms.
  • Patient-Reported Outcomes Measurement Information Systems (PROMIS) Anxiety Scale [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    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. We modified the instructions such that symptoms were rated over the past week. 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 as they indicate more frequent or more severe anxiety symptoms.
  • State Self-Esteem Scale Social Evaluation subscale (SSES-SE) [ Time Frame: Day 7 of Each Condition (Lab 2) ]
    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. We modified the instructions such that symptoms were rated over the past week. 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality
Official Title  ICMJE Ovarian Hormone Withdrawal and Suicide Risk: An Experimental Approach
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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Crossover 2-Condition Placebo-Controlled Trial
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Identical placebos provided by the UNC investigational drug service.
Primary Purpose: Basic Science
Condition  ICMJE Suicidal Ideation
Intervention  ICMJE
  • 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
    Other Name: Climara
  • Drug: Oral Micronized Progesterone
    100 mg oral micronized progesterone taken orally twice daily for 14 days starting day 7 after ovulation
    Other Name: Prometrium
  • Drug: Inactive Clear Patch
    Matching placebo patch administered by affixing to skin for 14 days starting on day 7 after ovulation
    Other Name: Placebo transdermal patch
  • Drug: Placebo capsule
    Matching placebo capsules administered twice daily for 14 days starting day 7 after ovulation
    Other Name: Sugar pill
Study Arms  ICMJE
  • Experimental: Active condition, then Inactive condition
    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.
    Interventions:
    • Drug: Estradiol Transdermal Patch 0.1 mg/24 hrs
    • Drug: Oral Micronized Progesterone
    • Drug: Inactive Clear Patch
    • Drug: Placebo capsule
  • Placebo Comparator: Inactive condition, then active condition
    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.
    Interventions:
    • Drug: Estradiol Transdermal Patch 0.1 mg/24 hrs
    • Drug: Oral Micronized Progesterone
    • Drug: Inactive Clear Patch
    • Drug: Placebo capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 18, 2019)
30
Original Actual Enrollment  ICMJE
 (submitted: October 24, 2018)
37
Actual Study Completion Date  ICMJE November 2017
Actual Primary Completion Date November 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Since the study is focused on the menstrual cycle, the study includes only those assigned female sex at birth.
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03720847
Other Study ID Numbers  ICMJE 16-2078
K99MH109667 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with the University of North Carolina (UNC) at Chapel Hill.
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
Responsible Party University of North Carolina, Chapel Hill
Study Sponsor  ICMJE University of North Carolina, Chapel Hill
Collaborators  ICMJE National Institute of Mental Health (NIMH)
Investigators  ICMJE
Principal Investigator: Tory A Eisenlohr-Moul, PhD University of North Carolina, Chapel Hill
Study Chair: Susan Girdler, PhD University of North Carolina, Chapel Hill
PRS Account University of North Carolina, Chapel Hill
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP