Back to resultsEffect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality
Primary Purpose
Suicidal Ideation
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Estradiol Transdermal Patch 0.1 mg/24 hrs
Oral Micronized Progesterone
Inactive Clear Patch
Placebo capsule
Sponsored by
About this trial
This is an interventional basic science trial for Suicidal Ideation focused on measuring Steroid hormones, Estradiol, Progesterone, Depression, Suicide
Eligibility Criteria
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.
Sites / Locations
- University of North Carolina at Chapel Hill
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Active condition, then Inactive condition
Inactive condition, then active condition
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT03720847
First Posted
October 24, 2018
Last Updated
January 18, 2019
Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT03720847
Brief Title
Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality
Official Title
Ovarian Hormone Withdrawal and Suicide Risk: An Experimental Approach
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
December 31, 2016 (Actual)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Suicidal Ideation
Keywords
Steroid hormones, Estradiol, Progesterone, Depression, Suicide
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
Crossover 2-Condition Placebo-Controlled Trial
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Identical placebos provided by the UNC investigational drug service.
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active condition, then Inactive condition
Arm Type
Experimental
Arm Description
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.
Arm Title
Inactive condition, then active condition
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Estradiol Transdermal Patch 0.1 mg/24 hrs
Other Intervention Name(s)
Climara
Intervention Description
Estradiol transdermal patch delivering 0.1 mg/24 hour administered by affixing to skin for 14 days starting on day 7 after ovulation
Intervention Type
Drug
Intervention Name(s)
Oral Micronized Progesterone
Other Intervention Name(s)
Prometrium
Intervention Description
100 mg oral micronized progesterone taken orally twice daily for 14 days starting day 7 after ovulation
Intervention Type
Drug
Intervention Name(s)
Inactive Clear Patch
Other Intervention Name(s)
Placebo transdermal patch
Intervention Description
Matching placebo patch administered by affixing to skin for 14 days starting on day 7 after ovulation
Intervention Type
Drug
Intervention Name(s)
Placebo capsule
Other Intervention Name(s)
Sugar pill
Intervention Description
Matching placebo capsules administered twice daily for 14 days starting day 7 after ovulation
Primary Outcome Measure Information:
Title
Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Ideation Score
Description
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.
Time Frame
Midluteal Baseline and Perimenstrual
Title
Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Planning Score
Description
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.
Time Frame
Midluteal Baseline and Perimenstrual
Secondary Outcome Measure Information:
Title
Perimenstrual Change in Beck Hopelessness Scale (BHS) Score
Description
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.
Time Frame
Day 7 of Each Condition (Lab 2)
Title
Perimenstrual Change in Center for Epidemiological Studies Depression Scale (CES-D) Score
Description
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.
Time Frame
Day 7 of Each Condition (Lab 2)
Title
Perimenstrual Change in Lack of Premeditation Subscale Score of the "Urgency, Premeditation, Perseverance, Sensation Seeking, and Positive Urgency (UPPSP) Impulsivity Scale"
Description
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.
Time Frame
Day 7 of Each Condition (Lab 2)
Title
Perimenstrual Changes in Patient-Reported Outcomes Measurement Information Systems (PROMIS) Anxiety Scale Score
Description
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.
Time Frame
Day 7 of Each Condition (Lab 2)
Title
Perimenstrual Change in State Self-Esteem Scale Social Evaluation Subscale (SSES-SE) Score
Description
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.
Time Frame
Day 7 of Each Condition (Lab 2)
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Since the study is focused on the menstrual cycle, the study includes only those assigned female sex at birth.
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tory A Eisenlohr-Moul, PhD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Susan Girdler, PhD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Study Chair
Facility Information:
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
60657
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
9 to 36 months following publication
IPD Sharing Access Criteria
Following execution of a data use/sharing agreement with the University of North Carolina at Chapel Hill
Learn more about this trial
Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality
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