Suicidal IdeationPhase 4NCT03720847
Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality
A Phase 4 study testing Estradiol Transdermal Patch 0.1 mg/24 hrs, Oral Micronized Progesterone and Inactive Clear Patch in people with Suicidal Ideation, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
This within-person, crossover, 2-condition, placebo-controlled study compares the impact of two perimenstrual conditions on severity of suicidal symptoms in females with past-month suicidality but minimal risk of imminent suicide attempt. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Suicidal Ideation
- What is being tested?
- Estradiol Transdermal Patch 0.1 mg/24 hrs, Oral Micronized Progesterone and Inactive Clear Patch
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Dec 2016to Nov 2017
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 60657
About this study
Official title: Ovarian Hormone Withdrawal and Suicide Risk: An Experimental Approach
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.
Read the 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.
- Conditions
- Suicidal Ideation
- Being tested
- Estradiol Transdermal Patch 0.1 mg/24 hrs, Oral Micronized Progesterone, Inactive Clear Patch, Placebo capsule
- Keywords
- Steroid hormones, Estradiol, Progesterone, Depression, Suicide
- Medical subject headings
- Suicidal Ideation, Depression, Suicide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol Transdermal Patch 0.1 mg/24 hrsDrug
Also called Climara
Estradiol transdermal patch delivering 0.1 mg/24 hour administered by affixing to skin for 14 days starting on day 7 after ovulation
Oral Micronized ProgesteroneDrug
Also called Prometrium
100 mg oral micronized progesterone taken orally twice daily for 14 days starting day 7 after ovulation
Inactive Clear PatchDrug
Also called Placebo transdermal patch
Matching placebo patch administered by affixing to skin for 14 days starting on day 7 after ovulation
Placebo capsuleDrug
Also called Sugar pill
Matching placebo capsules administered twice daily for 14 days starting day 7 after ovulation
| Study group | Role | What they receive |
|---|---|---|
| Active condition, then Inactive condition | Experimental | 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. Receives: Drug: Estradiol Transdermal Patch 0.1 mg/24 hrs; Drug: Oral Micronized Progesterone; Drug: Inactive Clear Patch; Drug: Placebo capsule |
| Inactive condition, then active condition | Placebo comparator | 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. Receives: Drug: Estradiol Transdermal Patch 0.1 mg/24 hrs; Drug: Oral Micronized Progesterone; Drug: Inactive Clear Patch; Drug: Placebo capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Midluteal Baseline and Perimenstrual
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.
Measured: Midluteal Baseline and Perimenstrual
Secondary outcomes (5)
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.
Measured: Day 7 of Each Condition (Lab 2)
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.
Measured: Day 7 of Each Condition (Lab 2)
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.
Measured: Day 7 of Each Condition (Lab 2)
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.
Measured: Day 7 of Each Condition (Lab 2)
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.
Measured: Day 7 of Each Condition (Lab 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start31 Dec 2016
- Primary completionNov 2017
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Suicidal IdeationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Crossover 2-Condition Placebo-Controlled Trial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Tory A Eisenlohr-Moul, PhD, Principal investigator, University of North Carolina, Chapel HillSusan Girdler, PhD, Study chair, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03720847
- Sponsor's protocol ID
- 16-2078
- Other IDs
- K99MH109667
- Status last verified
- Oct 2018
- First submitted
- 24 Oct 2018
- Last updated
- 4 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
Barone JC, Wenzel E, Alluri V, Moriarity D, Pinna G, Walsh E, Rubinow DR, Morrow AL, Eisenlohr-Moul TA. Effects of estrogen and progesterone on neuroactive steroids and cytokines in patients with suicidality. Psychoneuroendocrinology. 2023 Nov;157:106359. doi: 10.1016/j.psyneuen.2023.106359. Epub 2023 Aug 9.
PubMed 37611527Owens SA, Schmalenberger KM, Bowers S, Rubinow DR, Prinstein MJ, Girdler SS, Eisenlohr-Moul TA. Cyclical exacerbation of suicidal ideation in female outpatients: Prospective evidence from daily ratings in a transdiagnostic sample. J Psychopathol Clin Sci. 2023 Aug;132(6):704-715. doi: 10.1037/abn0000838. Epub 2023 Jun 15.
PubMed 37326562Eisenlohr-Moul TA, Bowers SM, Prinstein MJ, Schmalenberger KM, Walsh EC, Young SL, Rubinow DR, Girdler SS. Effects of acute estradiol and progesterone on perimenstrual exacerbation of suicidal ideation and related symptoms: a crossover randomized controlled trial. Transl Psychiatry. 2022 Dec 30;12(1):528. doi: 10.1038/s41398-022-02294-1.
PubMed 36585408