Trial Outcomes & Findings for Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality (NCT NCT03720847)
NCT ID: NCT03720847
Last Updated: 2019-02-04
Results Overview
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.
COMPLETED
PHASE4
30 participants
Midluteal Baseline and Perimenstrual
2019-02-04
Participant Flow
Recruitment occurred between November 15, 2016 and August 12, 2017. All participants were recruited via social media advertisements to participate in "a study on the biology of stress, depression, and suicidal thoughts". All participants were enrolled at the single site for the study: UNC Chapel Hill Psychiatry Department laboratories.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Condition 1
STARTED
|
15
|
15
|
|
Condition 1
COMPLETED
|
15
|
15
|
|
Condition 1
NOT COMPLETED
|
0
|
0
|
|
Washout
STARTED
|
15
|
15
|
|
Washout
COMPLETED
|
14
|
13
|
|
Washout
NOT COMPLETED
|
1
|
2
|
|
Condition 2
STARTED
|
14
|
13
|
|
Condition 2
COMPLETED
|
14
|
13
|
|
Condition 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Washout
Physician Decision
|
1
|
2
|
Baseline Characteristics
Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality
Baseline characteristics by cohort
| Measure |
Overall Study
n=30 Participants
All participants.
|
|---|---|
|
Age, Continuous
|
28.56 years
STANDARD_DEVIATION 1.09 • n=5 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Midluteal Baseline and PerimenstrualPopulation: All participants who were exposed to either 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). 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.
Outcome measures
| Measure |
Active Estradiol + Progesterone
n=28 Participants
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
|
Placebos
n=29 Participants
placebo patch + placebo pills twice daily.
|
|---|---|---|
|
Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Ideation Score
|
-.05 units on a scale
Standard Deviation .44
|
.35 units on a scale
Standard Deviation .18
|
PRIMARY outcome
Timeframe: Midluteal Baseline and PerimenstrualPopulation: All participants who were exposed to either condition.
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.
Outcome measures
| Measure |
Active Estradiol + Progesterone
n=28 Participants
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
|
Placebos
n=29 Participants
placebo patch + placebo pills twice daily.
|
|---|---|---|
|
Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Planning Score
|
-.06 units on a scale
Standard Deviation .26
|
.17 units on a scale
Standard Deviation .22
|
SECONDARY outcome
Timeframe: Day 7 of Each Condition (Lab 2)Population: All participants who were exposed to either condition.
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.
Outcome measures
| Measure |
Active Estradiol + Progesterone
n=29 Participants
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
|
Placebos
n=28 Participants
placebo patch + placebo pills twice daily.
|
|---|---|---|
|
Perimenstrual Change in Beck Hopelessness Scale (BHS) Score
|
-.017 units on a scale
Standard Deviation 2.42
|
1.37 units on a scale
Standard Deviation 2.72
|
SECONDARY outcome
Timeframe: Day 7 of Each Condition (Lab 2)Population: All participants who were exposed to either condition.
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.
Outcome measures
| Measure |
Active Estradiol + Progesterone
n=28 Participants
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
|
Placebos
n=29 Participants
placebo patch + placebo pills twice daily.
|
|---|---|---|
|
Perimenstrual Change in Center for Epidemiological Studies Depression Scale (CES-D) Score
|
-1.53 units on a scale
Standard Deviation 4.62
|
2.69 units on a scale
Standard Deviation 7.89
|
SECONDARY outcome
Timeframe: Day 7 of Each Condition (Lab 2)Population: All participants who were exposed to either condition.
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.
Outcome measures
| Measure |
Active Estradiol + Progesterone
n=29 Participants
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
|
Placebos
n=28 Participants
placebo patch + placebo pills twice daily.
|
|---|---|---|
|
Perimenstrual Change in Lack of Premeditation Subscale Score of the "Urgency, Premeditation, Perseverance, Sensation Seeking, and Positive Urgency (UPPSP) Impulsivity Scale"
|
-.75 units on a scale
Standard Deviation 1.75
|
.27 units on a scale
Standard Deviation 2.43
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Active Estradiol + Progesterone
n=28 Participants
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
|
Placebos
n=29 Participants
placebo patch + placebo pills twice daily.
|
|---|---|---|
|
Perimenstrual Changes in Patient-Reported Outcomes Measurement Information Systems (PROMIS) Anxiety Scale Score
|
1.39 units on a scale
Standard Deviation 2.80
|
.17 units on a scale
Standard Deviation 3.37
|
SECONDARY outcome
Timeframe: Day 7 of Each Condition (Lab 2)Population: All participants who were exposed to either condition.
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.
Outcome measures
| Measure |
Active Estradiol + Progesterone
n=29 Participants
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
|
Placebos
n=28 Participants
placebo patch + placebo pills twice daily.
|
|---|---|---|
|
Perimenstrual Change in State Self-Esteem Scale Social Evaluation Subscale (SSES-SE) Score
|
1.65 units on a scale
Standard Deviation 4.26
|
-.33 units on a scale
Standard Deviation 4.78
|
Adverse Events
Active Estradiol + Progesterone
Placebos
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Active Estradiol + Progesterone
n=28 participants at risk
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
|
Placebos
n=29 participants at risk
placebo patch + placebo pills twice daily.
|
|---|---|---|
|
General disorders
Skin Itching
|
28.6%
8/28 • Number of events 8 • The two weeks of patch/pill administration that occurred during each of the two conditions.
Assessed during daily study phone calls. Under "Participant Flow", Arm/Group is represented by two condition order categories (i.e., "Active Condition, then Inactive Condition" vs. "Inactive Condition, then Active Condition"); this allows one to understand effects of condition order on participant flow. Here, Arm/Group is represented as exposure to active vs. placebo conditions, since that is the relevant grouping to understand how placebo vs. active medication influenced risk of adverse events.
|
24.1%
7/29 • Number of events 7 • The two weeks of patch/pill administration that occurred during each of the two conditions.
Assessed during daily study phone calls. Under "Participant Flow", Arm/Group is represented by two condition order categories (i.e., "Active Condition, then Inactive Condition" vs. "Inactive Condition, then Active Condition"); this allows one to understand effects of condition order on participant flow. Here, Arm/Group is represented as exposure to active vs. placebo conditions, since that is the relevant grouping to understand how placebo vs. active medication influenced risk of adverse events.
|
|
General disorders
Breast Tenderness
|
28.6%
8/28 • Number of events 8 • The two weeks of patch/pill administration that occurred during each of the two conditions.
Assessed during daily study phone calls. Under "Participant Flow", Arm/Group is represented by two condition order categories (i.e., "Active Condition, then Inactive Condition" vs. "Inactive Condition, then Active Condition"); this allows one to understand effects of condition order on participant flow. Here, Arm/Group is represented as exposure to active vs. placebo conditions, since that is the relevant grouping to understand how placebo vs. active medication influenced risk of adverse events.
|
27.6%
8/29 • Number of events 8 • The two weeks of patch/pill administration that occurred during each of the two conditions.
Assessed during daily study phone calls. Under "Participant Flow", Arm/Group is represented by two condition order categories (i.e., "Active Condition, then Inactive Condition" vs. "Inactive Condition, then Active Condition"); this allows one to understand effects of condition order on participant flow. Here, Arm/Group is represented as exposure to active vs. placebo conditions, since that is the relevant grouping to understand how placebo vs. active medication influenced risk of adverse events.
|
|
General disorders
Headache
|
17.9%
5/28 • Number of events 5 • The two weeks of patch/pill administration that occurred during each of the two conditions.
Assessed during daily study phone calls. Under "Participant Flow", Arm/Group is represented by two condition order categories (i.e., "Active Condition, then Inactive Condition" vs. "Inactive Condition, then Active Condition"); this allows one to understand effects of condition order on participant flow. Here, Arm/Group is represented as exposure to active vs. placebo conditions, since that is the relevant grouping to understand how placebo vs. active medication influenced risk of adverse events.
|
31.0%
9/29 • Number of events 9 • The two weeks of patch/pill administration that occurred during each of the two conditions.
Assessed during daily study phone calls. Under "Participant Flow", Arm/Group is represented by two condition order categories (i.e., "Active Condition, then Inactive Condition" vs. "Inactive Condition, then Active Condition"); this allows one to understand effects of condition order on participant flow. Here, Arm/Group is represented as exposure to active vs. placebo conditions, since that is the relevant grouping to understand how placebo vs. active medication influenced risk of adverse events.
|
|
General disorders
Nausea
|
7.1%
2/28 • Number of events 2 • The two weeks of patch/pill administration that occurred during each of the two conditions.
Assessed during daily study phone calls. Under "Participant Flow", Arm/Group is represented by two condition order categories (i.e., "Active Condition, then Inactive Condition" vs. "Inactive Condition, then Active Condition"); this allows one to understand effects of condition order on participant flow. Here, Arm/Group is represented as exposure to active vs. placebo conditions, since that is the relevant grouping to understand how placebo vs. active medication influenced risk of adverse events.
|
3.4%
1/29 • Number of events 1 • The two weeks of patch/pill administration that occurred during each of the two conditions.
Assessed during daily study phone calls. Under "Participant Flow", Arm/Group is represented by two condition order categories (i.e., "Active Condition, then Inactive Condition" vs. "Inactive Condition, then Active Condition"); this allows one to understand effects of condition order on participant flow. Here, Arm/Group is represented as exposure to active vs. placebo conditions, since that is the relevant grouping to understand how placebo vs. active medication influenced risk of adverse events.
|
Additional Information
Tory Eisenlohr-Moul
University of North Carolina at Chapel Hill
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place