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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Basic Science
Condition Suicidal Ideation
Interventions Drug: Estradiol Transdermal Patch 0.1 mg/24 hrs
Drug: Oral Micronized Progesterone
Drug: Inactive Clear Patch
Drug: Placebo capsule
Enrollment 30
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Active Condition, Then Inactive Condition Inactive Condition, Then Active Condition
Hide Arm/Group 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.
Period Title: Condition 1
Started 15 15
Completed 15 15
Not Completed 0 0
Period Title: Washout
Started 15 15
Completed 14 13
Not Completed 1 2
Reason Not Completed
Physician Decision             1             2
Period Title: Condition 2
Started 14 13
Completed 14 13
Not Completed 0 0
Arm/Group Title Overall Study
Hide Arm/Group Description All participants.
Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants
28.56  (1.09)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
30
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Hispanic or Latino
1
   3.3%
Not Hispanic or Latino
29
  96.7%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   3.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   3.3%
White
27
  90.0%
More than one race
1
   3.3%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
 100.0%
1.Primary Outcome
Title Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Ideation Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were exposed to either condition.
Arm/Group Title Active Estradiol + Progesterone Placebos
Hide Arm/Group Description:
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
placebo patch + placebo pills twice daily.
Overall Number of Participants Analyzed 28 29
Mean (Standard Deviation)
Unit of Measure: units on a scale
-.05  (.44) .35  (.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Estradiol + Progesterone, Placebos
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .012
Comments [Not Specified]
Method t-test, 2 sided
Comments paired sample t-test comparing perimenstrual change in the placebo vs. active conditions within a given participant.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value .26
Estimation Comments Positive estimated value indicates greater perimenstrual increase in symptoms in the placebo condition relative to the active condition.
2.Primary Outcome
Title Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Planning Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were exposed to either condition.
Arm/Group Title Active Estradiol and Progesterone Placebos
Hide Arm/Group Description:
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
placebo patch + placebo pills twice daily.
Overall Number of Participants Analyzed 28 29
Mean (Standard Deviation)
Unit of Measure: units on a scale
-.06  (.26) .17  (.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Estradiol and Progesterone, Placebos
Comments paired sample t-test comparing perimenstrual change in the placebo vs. active conditions within a given participant.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .030
Comments [Not Specified]
Method t-test, 2 sided
Comments paired sample t-test comparing perimenstrual change in the placebo vs. active conditions within a given participant.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value .21
Estimation Comments Positive estimated value indicates a greater perimenstrual increase in the outcome in the placebo condition relative to the active condition.
3.Secondary Outcome
Title Perimenstrual Change in Beck Hopelessness Scale (BHS) Score
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were exposed to either condition.
Arm/Group Title Active Estradiol and Progesterone Placebos
Hide Arm/Group Description:
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
placebo patch + placebo pills twice daily.
Overall Number of Participants Analyzed 29 28
Mean (Standard Deviation)
Unit of Measure: units on a scale
-.017  (2.42) 1.37  (2.72)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Estradiol and Progesterone, Placebos
Comments paired sample t-test comparing perimenstrual change in the placebo vs. active conditions within a given participant.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .013
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.16
Estimation Comments Positive estimated value indicates greater perimenstrual increase in symptoms in the placebo condition relative to the active condition.
4.Secondary Outcome
Title Perimenstrual Change in Center for Epidemiological Studies Depression Scale (CES-D) Score
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were exposed to either condition.
Arm/Group Title Active Estradiol and Progesterone Placebos
Hide Arm/Group Description:
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
placebo patch + placebo pills twice daily.
Overall Number of Participants Analyzed 28 29
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.53  (4.62) 2.69  (7.89)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Estradiol and Progesterone, Placebos
Comments paired sample t-test comparing perimenstrual change in the placebo vs. active conditions within a given participant.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .018
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.65
Estimation Comments Positive estimated value indicates greater perimenstrual change in the placebo condition relative to the active condition.
5.Secondary Outcome
Title Perimenstrual Change in Lack of Premeditation Subscale Score of the "Urgency, Premeditation, Perseverance, Sensation Seeking, and Positive Urgency (UPPSP) Impulsivity Scale"
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were exposed to either condition.
Arm/Group Title Active Estradiol and Progesterone Placebos
Hide Arm/Group Description:
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
placebo patch + placebo pills twice daily.
Overall Number of Participants Analyzed 29 28
Mean (Standard Deviation)
Unit of Measure: units on a scale
-.75  (1.75) .27  (2.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Estradiol and Progesterone, Placebos
Comments paired sample t-test comparing perimenstrual change in the placebo vs. active conditions within a given participant.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .073
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.04
Estimation Comments Positive estimated value indicates greater perimenstrual increase in symptoms in the placebo condition relative to the active condition.
6.Secondary Outcome
Title Perimenstrual Changes in Patient-Reported Outcomes Measurement Information Systems (PROMIS) Anxiety Scale Score
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Estradiol and Progesterone Placebos
Hide Arm/Group Description:
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
placebo patch + placebo pills twice daily.
Overall Number of Participants Analyzed 28 29
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.39  (2.80) .17  (3.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Estradiol and Progesterone, Placebos
Comments paired sample t-test comparing perimenstrual change in the placebo vs. active conditions within a given participant.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .25
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.16
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Perimenstrual Change in State Self-Esteem Scale Social Evaluation Subscale (SSES-SE) Score
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were exposed to either condition.
Arm/Group Title Active Estradiol and Progesterone Placebos
Hide Arm/Group Description:
.1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day).
placebo patch + placebo pills twice daily.
Overall Number of Participants Analyzed 29 28
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.65  (4.26) -.33  (4.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Estradiol and Progesterone, Placebos
Comments paired sample t-test comparing perimenstrual change in the placebo vs. active conditions within a given participant.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .23
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.32
Estimation Comments [Not Specified]
Time Frame The two weeks of patch/pill administration that occurred during each of the two conditions.
Adverse Event Reporting Description 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.
 
Arm/Group Title Active Estradiol + Progesterone Placebos
Hide Arm/Group Description .1mg/day of transdermal estradiol + 100mg oral micronized progesterone twice daily (200mg/day). placebo patch + placebo pills twice daily.
All-Cause Mortality
Active Estradiol + Progesterone Placebos
Affected / at Risk (%) Affected / at Risk (%)
Total   0/28 (0.00%)      0/29 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Active Estradiol + Progesterone Placebos
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/28 (0.00%)      0/29 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Active Estradiol + Progesterone Placebos
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/28 (53.57%)      18/29 (62.07%)    
General disorders     
Skin Itching  1 [1]  8/28 (28.57%)  8 7/29 (24.14%)  7
Breast Tenderness  1  8/28 (28.57%)  8 8/29 (27.59%)  8
Headache  1  5/28 (17.86%)  5 9/29 (31.03%)  9
Nausea  1  2/28 (7.14%)  2 1/29 (3.45%)  1
1
Term from vocabulary, MedDRA (10.0)
Indicates events were collected by systematic assessment
[1]
Itching around patch.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Tory Eisenlohr-Moul
Organization: University of North Carolina at Chapel Hill
Phone: 859-317-0503
EMail: moul@med.unc.edu
Layout table for additonal information
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03720847     History of Changes
Other Study ID Numbers: 16-2078
K99MH109667 ( U.S. NIH Grant/Contract )
First Submitted: October 24, 2018
First Posted: October 25, 2018
Results First Submitted: November 15, 2018
Results First Posted: February 4, 2019
Last Update Posted: February 4, 2019