Primary outcomeMean· up to 6 weeks
Mean Threat Processing Bias During Visual Dot-probe Paradigm Over Time
| Group | Value (attention bias in milliseconds) | Spread |
|---|---|---|
| Hormone Sensitive Women (HS+) | -0.57 | 18.92 |
| Hormone Insensitive Women (HS-) | 36.92 | 110.98 |
Trial · Interventional
CompletedPhase 2Results postedRegistry dataCharacterizing the Neural Substrates of Irritability in Women: an Experimental Neuroendocrine Model
Overview
- Status
- Completed
- Phase
- Phase 2
- Enrollment
- 23 participants (actual)
- Sponsor
- University of North Carolina, Chapel Hill · Other
- Design
- Not randomized · Double masking
- Countries
1 country
United States
- Start
- 2 Jan 2020
- Primary completion
- 15 Jul 2022
- Completion
- 19 Jul 2022
- First posted
- 9 Aug 2019
- Last update posted
- 25 Aug 2023
- Conditions
- Perinatal Depression · Post Partum Depression · Depression, Postpartum · Depression
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
2020202120222023
- Ph 2
Characterizing the Neural Substrates of Irritability in Women: an Experimental Neuroendocrine Model
NCT040513202 Jan 2020 to 19 Jul 2022
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
The proposed study involves experimentally manipulating reproductive hormones in nonpregnant, euthymic women to create a scaled down version of the changes that occur during pregnancy and the postpartum period. This endocrine manipulation paradigm, which the investigators have shown provokes irritability in past studies, will be used to examine the neurocircuitry underlying irritability under baseline and hormone challenge conditions among women who are hormone sensitive (HS+; n=15) and non-hormone sensitive (HS-; n=15). The long-term goal of this research is to advance understanding of the neural systems underlying both the triggering of and susceptibility to irritability in women. The objective of the current project is to examine whether HS+ show differences in the behavioral activation system relative to HS- under baseline and hormone challenge conditions using functional magnetic resonance imaging (fMRI) and behavioral tests.
Interventions
- Leuprolide Acetate 3.75 MG/MLDrug
- Estradiol 2 Mg tabletDrug
- Micronized progesteroneDrug
Arms2
Experimental
Hormone Sensitive Women (HS+)
Participants will take leuprolide acetate (lupron) via intramuscular injection, for 2 months. Participants will take 2 mg of estradiol twice daily and 200 mg of progesterone twice daily for 2 weeks.
Experimental
Hormone Insensitive Women (HS-)
Participants will take leuprolide acetate (lupron) via intramuscular injection, for 2 months. Participants will take 2 mg of estradiol twice daily and 200 mg of progesterone twice daily for 2 weeks.
Primary outcomes12
Outcomes the sponsor listed as primary.
Mean Threat Processing Bias During Visual Dot-probe Paradigm Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which irritability is characterized by dysfunctional threat processing during reproductive hormone challenge relative to baseline in HS+ and HS- by examining threat attention bias assessed during the visual dot-probe paradigm. The Visual Dot-Probe Paradigm asks participants to detect a target stimulus that is embedded in a matrix of distracting stimuli (e.g., a target stimulus, an angry face, might be embedded in a matrix of neutral distractor faces). Attention biases are inferred from faster response times to detect a threatening stimulus in a matrix of neutral stimuli relative to response time to detect neutral stimuli in neutral matrices. Thus, positive times reflect attention bias toward threat, whereas negative times reflect attention bias away from threat.
Mean Right Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which irritability is characterized by dysfunctional threat processing during reproductive hormone challenge relative to baseline in HS+ and HS-. By examining amygdala-medial prefrontal cortex (PFC) Blood-oxygen-level-dependent (BOLD) connectivity in response to threatening faces on the implicit emotion face processing fMRI task in HS+ (compared with HS-) during hormone challenge relative to baseline. The implicit emotion face processing task asks participants to identify the gender of angry, happy, and fearful faces at 50%, 100% and 150% emotion intensity presented in random order for 2000 milliseconds followed by jittered fixation. Trials appear in 3 blocks, generating 30 trials of each emotion at each intensity and 90 neutral face emotion trials.
Mean Left Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which irritability is characterized by dysfunctional threat processing during reproductive hormone challenge relative to baseline in HS+ and HS-. By examining amygdala-medial prefrontal cortex (PFC) connectivity in response to threatening faces on the implicit emotion face processing fMRI task in HS+ (compared with HS-) during hormone challenge relative to baseline. The implicit emotion face processing task asks participants to identify the gender of angry, happy, and fearful faces at 50%, 100% and 150% emotion intensity presented in random order for 2000 milliseconds followed by jittered fixation. Trials appear in 3 blocks, generating 30 trials of each emotion at each intensity and 90 neutral face emotion trials.
Mean Reactive Aggression During Hormone Addback Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which HS+ is characterized by reactive aggression during hormone addback relative to baseline in the target population. Reactive aggression will be defined as the number of point subtractions the participant makes during the Point Subtraction Aggression Paradigm. Point Subtraction Aggression Paradigm measures relational aggression (approach behavior) in response to frustration. In the task, participants are asked to press a button to accrue money or press another button to subtract money from a (fictional) partner at no direct gain to themselves. Frustration is induced by periodic subtractions of their own money, which is attributed to the partner.
Mean BOLD Activation of the Right Amygdala During the Affective Posner Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right amygdala in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Mean BOLD Activation of the Left Amygdala During the Affective Posner Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left amygdala in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Mean BOLD Activation of the Right Caudate During the Affective Posner Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right caudate in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Mean BOLD Activation of the Left Caudate During the Affective Posner Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left caudate in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Mean BOLD Activation of the Right Putamen During the Affective Posner Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right putamen in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Mean BOLD Activation of the Left Putamen During the Affective Posner Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left putamen in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Mean BOLD Activation of the Right Nucleus Accumbens During the Affective Posner Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the right nucleus accumbens in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Mean BOLD Activation of the Left Nucleus Accumbens During the Affective Posner Task Over Time
Time frame · up to 6 weeks
Registry description
This outcome measure determines the extent to which HS+ is characterized by BOLD activation of the left nucleus accumbens in response to frustrative non-reward (FNR) in the Affective Posner Task during hormone addback relative to baseline in the target population. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Secondary outcomes(5)
Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill -0.8Scale and Threat Attention Bias
Time frame · Endpoint (week 6)
Registry description
This outcome measure determines the extent to which irritability is characterized by dysfunctional reward processing during reproductive hormone challenge in HS+ and HS- by examining the correlation between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper (i.e., irritability) Scale and threat attention bias.
Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Right Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity.
Time frame · Endpoint (week 6)
Registry description
This outcome measure determines the extent to which irritability is characterized by dysfunctional reward processing during reproductive hormone challenge in HS+ and HS- by examining the correlation between the IDAS Ill Temper (i.e., irritability) Scale and amygdala-medial PFC connectivity in HS+.
Correlation Between the Inventory of Depressive and Anxiety Symptoms (IDAS) Ill Temper Scale and Left Amygdala-medial Prefrontal Cortex (PFC) BOLD Connectivity.
Time frame · Endpoint (week 6)
Registry description
This outcome measure determines the extent to which irritability is characterized by dysfunctional reward processing during reproductive hormone challenge in HS+ and HS- by examining the correlation between the IDAS Ill Temper (i.e., irritability) Scale and amygdala-medial PFC connectivity in HS+.
Correlation Between Irritability and Reactive Aggression During Hormone Addback
Time frame · Endpoint (week 6)
Registry description
This outcome measure determines the degree of irritability and reactive aggression in HS+ during hormone addback and its relationship to the target population. Irritability will be defined as score on the IDAS Ill Temper Scale. Reactive aggression will be defined as the number of point subtractions the participant makes during the Point Subtraction Aggression Paradigm. The Point Subtraction Aggression Paradigm measures relational aggression (approach behavior) in response to frustration. In the task, participants are asked to press a button to ac
Correlation Between Irritability Subcortical Activation in HS+ During Hormone Addback
Time frame · Endpoint (week 6)
Registry description
This outcome measure determines the degree of subcortical (amygdala, caudate, putamen, and nucleus accumbens) activation in HS+ during hormone addback and it's relationship to the target population. The activation in amygdala and ventral striatum (caudate, putamen, nucleus accumbens) regions of interest (ROIs) will be assessed during the Affective Posner Task. The Affective Posner Task tests whether HS+ is characterized by reduced subcortical activation in response to frustration. This task is divided into 3 runs: during Run 1 (practice run), participants receive accurate feedback about their performance on the task and do not win or lose money; during Run 2, participants receive accurate feedback about their performance and win or lose 50 cents per trial; and during Run 3 (frustration), participants are told they must respond accurately to win money, but participants are given feedback that they responded too slowly on 60% of accurate trials, regardless of their performance.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Primary outcomeMean· up to 6 weeks
Mean Right Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time
| Group | Value (arbitrary units) | Spread |
|---|---|---|
| Hormone Sensitive Women (HS+) | 0.0174 | 0.0606 |
| Hormone Insensitive Women (HS-) | 0.0533 | 0.0338 |
Primary outcomeMean· up to 6 weeks
Mean Left Amygdala-medial Prefrontal Cortex BOLD Connectivity During Implicit Emotion Face Processing Task Over Time
| Group | Value (arbitrary units) | Spread |
|---|---|---|
| Hormone Sensitive Women (HS+) | 0.0247 | 0.0653 |
| Hormone Insensitive Women (HS-) | 0.0213 | 0.0374 |
Primary outcomeMean· up to 6 weeks
Mean Reactive Aggression During Hormone Addback Over Time
| Group | Value (Number of subtraction responses) | Spread |
|---|---|---|
| Hormone Sensitive Women (HS+) | 103.08 | 121.68 |
| Hormone Insensitive Women (HS-) | 129.20 | 105.76 |
Primary outcomeMean· up to 6 weeks
Mean BOLD Activation of the Right Amygdala During the Affective Posner Task Over Time
| Group | Value (Arbitrary Units) | Spread |
|---|---|---|
| Hormone Sensitive Women (HS+) | -0.04544 | 0.100148 |
| Hormone Insensitive Women (HS-) | 0.037334 | 0.137479 |
Primary outcomeMean· up to 6 weeks
Mean BOLD Activation of the Left Amygdala During the Affective Posner Task Over Time
| Group | Value (Arbitrary Units) | Spread |
|---|---|---|
| Hormone Sensitive Women (HS+) | 0.005316917 | 0.10109272 |
| Hormone Insensitive Women (HS-) | -0.009866667 | 0.12208237 |
Primary outcomeMean· up to 6 weeks
Mean BOLD Activation of the Right Caudate During the Affective Posner Task Over Time
| Group | Value (Arbitrary Units) | Spread |
|---|---|---|
| Hormone Sensitive Women (HS+) | -0.069919077 | 0.11155759 |
| Hormone Insensitive Women (HS-) | 0.061407 | 0.15720728 |
Primary outcomeMean· up to 6 weeks
Mean BOLD Activation of the Left Caudate During the Affective Posner Task Over Time
| Group | Value (Arbitrary Units) | Spread |
|---|---|---|
| Hormone Sensitive Women (HS+) | -0.043943333 | 0.19455199 |
| Hormone Insensitive Women (HS-) | 0.0077258 | 0.18794868 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Hormone Sensitive Women (HS+)Participants will take leuprolide acetate (lupron) via intramuscular injection, for 2 months. Participants will take 2 mg of estradiol twice daily and 200 mg of progesterone twice daily for 2 weeks. Leuprolide Acetate 3.75 MG/ML: 3.75 mg/month leuprolide acetate intramuscular injection Estradiol 2 Mg tablet: 2 mg estradiol tablet Micronized progesterone: 200 mg micronized progesterone tablets | 0 / 13 | 0 / 13 | 12 / 13 |
| Hormone Insensitive Women (HS-)Participants will take leuprolide acetate (lupron) via intramuscular injection, for 2 months. Participants will take 2 mg of estradiol twice daily and 200 mg of progesterone twice daily for 2 weeks. Leuprolide Acetate 3.75 MG/ML: 3.75 mg/month leuprolide acetate intramuscular injection Estradiol 2 Mg tablet: 2 mg estradiol tablet Micronized progesterone: 200 mg micronized progesterone tablets | 0 / 10 | 0 / 10 | 9 / 10 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies6
Studies that cite this trial.
Studies with results
1 study on this page
Indexing hint: Randomized controlled trial · 1998
2 results
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Full text at the publisher2 results
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Rights unknown
PubMed tag: none · 2005
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PubMed tag: none · 1997
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Leibenluft et al. 1997The Journal of clinical endocrinology and metabolismcited by 18
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Full text at the publisher
Eligibility
Who could join, as posted.
- Sex
- Female
- Age
- from 22 Years up to 45 Years
- Healthy volunteers
- Accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria:
Participants will include healthy, euthymic 22-45 year old women with a history of postpartum depression (n=15) and women without such a history (n=15). Thus, only participants capable of giving informed consent will be enrolled. Participants will be compensated upon completion of the study.
Inclusion Criteria. Group 1: Women with a history of perinatal depression
* A history of a the Diagnostic Statistic Manual of Mental Disorders - fifth edition (DSM-V) major depression episode that occurred within 6 weeks of childbirth (as determined by a SCID interview) and remitted at least one year prior to enrollment in the study;
* has been well for a minimum of one year;
* a regular menstrual cycle for at least three months;
* age 22-45;
* medication free (including birth control pills);.
Group 2: Healthy Controls
* Controls will meet all inclusion criteria specified above except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders.
A structured clinical interview for DSM-V (SCID) will be administered to all women prior to study entry. Any woman with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.
Exclusion Criteria:
Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any of the following:
* current axis I psychiatric diagnosis (based on a structured clinical interview for DSM-V (SCID);
* endometriosis;
* undiagnosed enlargement of the ovaries;
* liver disease;
* breast cancer;
* a history of blood clots in the legs or lungs;
* undiagnosed vaginal bleeding;
* porphyria;
* diabetes mellitus;
* malignant melanoma;
* gallbladder or pancreatic disease;
* heart or kidney disease;
* cerebrovascular disease (stroke);
* cigarette smoking;
* a history of suicide attempts or psychotic episodes requiring hospitalization;
* recurrent migraine with aura;
* pregnancy-related medical conditions such as hyperemesis gravidarum, preeclampsia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis;
* Any woman with a first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol;
Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for perimenopause will be excluded from participation. Specifically, the investigators will exclude any woman with an elevated plasma follicle stimulating hormone (FSH) level (\> 14 IU/L) and with menstrual cycle variability of \> 7 days different from their normal cycle length.
Pregnant women will be excluded from participation (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods), and women who become pregnant (although unlikely because of the hormone manipulation) will be withdrawn. The use of leuprolide acetate is not recommended during pregnancy. Prior to treatment, a complete physical, including a serum β-human chorionic gonadotropin (HCG) test for pregnancy. Participants will be seen at the outpatient clinic on a regular biweekly basis. All participants will be required to use non-hormonal forms of birth control (e.g., barrier methods) to avoid pregnancy during this study. Participants will also undergo urine toxicology and pregnancy tests on the day of each of the two fMRI scans. If a woman becomes pregnant during the study, she will not complete the fMRI scan, and the hormone protocol will be discontinued.
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