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| ID | Type | Description | Link |
|---|---|---|---|
| 1K23MH107831-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This study that aims to evaluate the psychophysiology of premenstrual mood disorders (PMDs) at baseline and after treatment with sertraline. Participants will include women with PMDs and healthy female controls. Participation involves a baseline visit to determine eligibility and three study visits that include questionnaires and stress reactivity assessment via an acoustic startle paradigm. Female participants with PMDs will receive sertraline during the premenstrual phase.
Among women with premenstrual mood dysphoric disorder (PMDD), baseline arousal is heightened during the luteal phase of the menstrual cycle compared to the follicular phase, as measured by acoustic startle response (ASR). Healthy female controls do not show cyclic changes in this measure of physiologic arousal. It has been suggested that such heightened physiologic arousal during the luteal phase may be due to differences in neurosteroid modulation of Gamma-aminobutyric acid (GABA)-A receptor function. Research indicates that women with premenstrual mood disorders (PMDs) may have sub-optimal sensitivity to the progesterone metabolite allopregnanolone (ALLO), a GABA-A receptor modulator. In animal models, intracerebroventricular injection of corticotrophin releasing factor (CRF) increases amplitude of the acoustic startle response, while ALLO administration attenuates this CRF-enhanced startle. The primary aim of this study is to examine differences in ASR by menstrual cycle phase (follicular, luteal) and group (control, PMDD). Secondary aim is to examine the impact of luteal phase treatment with a selective serotonin reuptake inhibitor (SSRI) on psychophysiology in women with PMDs. An exploratory aim is to examine immune function among these women.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sertraline | Experimental | To determine the impact of short term luteal phase treatment with Sertraline 50mg tablets (PMDD group only) on acoustic startle response across the menstrual cycle. Sertraline 50 mg tablets are administered daily from ovulation until menses onset. |
|
| Control | No Intervention | No intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sertraline | Drug | Sertraline will be provided at a dose of 50 mg daily for up to 3 weeks, depending on the length of a woman's luteal phase. Medication will be taken only during the luteal phase. Women will initiate sertraline treatment upon determining that they have ovulated (using a urine luteinizing hormone (LH) Kit) and remain on sertraline until onset of their next menstrual period at which time they will stop taking the medication. |
| Measure | Description | Time Frame |
|---|---|---|
| Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase | Acoustic startle response (ASR) is measured during the follicular and luteal phase of the menstrual cycle in controls and those with PMDD. Magnitude of ASR is measured using the eyeblink reflex, by recording activity from the orbicularis oculi muscle. Recording is performed via two surface disk electrodes (Ag-AgCl) applied underneath the left eye; one in line with the pupil and one 1-2 cm lateral to the first one. For the primary outcome of baseline ASR magnitude over the menstrual cycle, peak amplitude of the blink reflex was determined in the 20-120-ms time frame following stimulus onset relative to baseline (baseline is the average baseline electromyography (EMG) level for the 50 ms immediately preceding auditory stimulus onset). ASR is measured in microvolts, and raw ASR results are standardized to t-scores. Higher ASR t-score indicates greater contraction of the the orbicularis oculi muscle. A t-score of 50 indicates the population mean with a standard deviation of 10. | Month 1 (Follicular), Month 2 (Luteal) |
| Impact of Sertraline on ASR Magnitude | This outcome examines the impact of luteal phase treatment with a selective serotonin reuptake inhibitor (SSRI) (PMDD group only) on acoustic startle response (ASR). ASR is measured using the eyeblink reflex, measured by recording activity from the orbicularis oculi muscle. Recording is performed via two surface disk electrodes (Ag-AgCl) applied underneath the left eye; one in line with the pupil and one 1-2 cm lateral to the first one. Peak amplitude of the blink reflex is determined in the 20-120-ms time frame following stimulus onset. PMDD participants complete test day 3 (Luteal Month 3) while on sertraline and their ASR magnitude will be compared to their previous luteal test day (Luteal Month 2). ASR is measured in microvolts, and raw ASR results are standardized to t-scores. Higher ASR t-score indicates greater contraction of the the orbicularis oculi muscle. A t-score of 50 indicates the population mean with a standard deviation of 10. | Month 2 (Luteal), Month 3 (Luteal) |
| Measure | Description | Time Frame |
|---|---|---|
| Interleukin 6 (IL-6) Level | Blood samples were collected to measure serum interleukin-6 (IL-6). IL-6 levels were compared in the follicular and luteal phases, between Control and PMDD groups. Levels are measured in picogram/milliliter (pg/mL). | Month 1 (Follicular ), Month 2 (Luteal ) |
| Tumor Necrosis Factor Alpha (TNF-alpha) Level |
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Inclusion Criteria:
Participants must be:
Exclusion Criteria:
Participants cannot have:
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| Name | Affiliation | Role |
|---|---|---|
| Liisa Hantsoo, PhD | Assistant Professor | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Women's Reproductive Mental Health, Johns Hopkins University School of Medicine | Baltimore | Maryland | 21205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17314917 | Background | Epperson CN, Pittman B, Czarkowski KA, Stiklus S, Krystal JH, Grillon C. Luteal-phase accentuation of acoustic startle response in women with premenstrual dysphoric disorder. Neuropsychopharmacology. 2007 Oct;32(10):2190-8. doi: 10.1038/sj.npp.1301351. Epub 2007 Feb 21. | |
| 26377947 | Background | Hantsoo L, Epperson CN. Premenstrual Dysphoric Disorder: Epidemiology and Treatment. Curr Psychiatry Rep. 2015 Nov;17(11):87. doi: 10.1007/s11920-015-0628-3. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Control | Controls do not receive sertraline. |
| FG001 | Sertraline | To determine the impact of short term luteal phase treatment with Sertraline 50mg tablets (PMD group only) on arousal regulation across the menstrual cycle. Sertraline: Sertraline will be provided at a dose of 50 mg daily for up to 3 weeks, depending on the length of a woman's luteal phase. Medication will be taken only during the luteal phase. Women will initiate sertraline treatment upon determining that they have ovulated (using a urine luteinizing hormone (LH) Kit) and remain on sertraline until onset of their next menstrual period at which time they will stop taking the medication. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Control | Controls do not receive sertraline. |
| BG001 | Sertraline | To determine the impact of short term luteal phase treatment with Sertraline 50mg tablets (PMD group only) on arousal regulation across the menstrual cycle. Sertraline: Sertraline will be provided at a dose of 50 mg daily for up to 3 weeks, depending on the length of a woman's luteal phase. Medication will be taken only during the luteal phase. Women will initiate sertraline treatment upon determining that they have ovulated (using a urine LH Kit) and remain on sertraline until onset of their next menstrual period at which time they will stop taking the medication. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase | Acoustic startle response (ASR) is measured during the follicular and luteal phase of the menstrual cycle in controls and those with PMDD. Magnitude of ASR is measured using the eyeblink reflex, by recording activity from the orbicularis oculi muscle. Recording is performed via two surface disk electrodes (Ag-AgCl) applied underneath the left eye; one in line with the pupil and one 1-2 cm lateral to the first one. For the primary outcome of baseline ASR magnitude over the menstrual cycle, peak amplitude of the blink reflex was determined in the 20-120-ms time frame following stimulus onset relative to baseline (baseline is the average baseline electromyography (EMG) level for the 50 ms immediately preceding auditory stimulus onset). ASR is measured in microvolts, and raw ASR results are standardized to t-scores. Higher ASR t-score indicates greater contraction of the the orbicularis oculi muscle. A t-score of 50 indicates the population mean with a standard deviation of 10. | 33 Controls and 24 PMDD (Sertraline) completed the Month 1 (Follicular) visit, and 27 Controls and 23 premenstrual mood dysphoric disorder (PMDD) completed the Month 2 (Luteal) visit. Assessments were done on 1 day of the Follicular phase and 1 day of the Luteal phase. | Posted | Mean | Standard Deviation | t score | Month 1 (Follicular), Month 2 (Luteal) |
1 month
Participants in the control arm were not assessed for adverse events since they did not receive an intervention. Only 23 participants in the sertraline arm stayed on study to be assessed for adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control | Controls do not receive sertraline. | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Liisa Hantsoo, Ph.D. | The Johns Hopkins University School of Medicine | 410-502-2334 | LHantso1@jh.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 1, 2022 | Sep 6, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011293 | Premenstrual Syndrome |
| ID | Term |
|---|---|
| D008599 | Menstruation Disturbances |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D020280 | Sertraline |
| ID | Term |
|---|---|
| D015057 | 1-Naphthylamine |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009281 | Naphthalenes |
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Blood samples were collected to measure serum TNF-alpha levels in the Follicular and Luteal 1 phases. Levels are measured in picogram/milliliter (pg/mL). |
| Month 1 (Follicular ), Month 2 (Luteal ) |
| 28041003 | Background | Epperson CN, Hantsoo LV. Making Strides to Simplify Diagnosis of Premenstrual Dysphoric Disorder. Am J Psychiatry. 2017 Jan 1;174(1):6-7. doi: 10.1176/appi.ajp.2016.16101144. No abstract available. |
| 29777410 | Background | Hantsoo L, Golden CEM, Kornfield S, Grillon C, Epperson CN. Startling Differences: Using the Acoustic Startle Response to Study Sex Differences and Neurosteroids in Affective Disorders. Curr Psychiatry Rep. 2018 May 18;20(6):40. doi: 10.1007/s11920-018-0906-y. |
| 32435664 | Background | Hantsoo L, Epperson CN. Allopregnanolone in premenstrual dysphoric disorder (PMDD): Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle. Neurobiol Stress. 2020 Feb 4;12:100213. doi: 10.1016/j.ynstr.2020.100213. eCollection 2020 May. |
| Result | Hantsoo, L., Kaminsky, Z., Payne, J.L. Luteal Phase Epigenetic Biomarkers Identify Premenstrual Dysphoric Disorder (PMDD) and Selective Serotonin Reuptake Inhibitor (SSRI) Response in PMDD. Neuropsychopharmacology (2022) 47:220 - 370. |
| 38091917 | Result | Miller KN, Standeven L, Morrow AL, Payne JL, Epperson CN, Hantsoo L. GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder. Psychoneuroendocrinology. 2024 Feb;160:106684. doi: 10.1016/j.psyneuen.2023.106684. Epub 2023 Nov 30. |
| 39096755 | Result | Barone JC, Ho A, Osborne LM, Eisenlohr-Moul TA, Morrow AL, Payne JL, Epperson CN, Hantsoo L. Luteal phase sertraline treatment of premenstrual dysphoric disorder (PMDD): Effects on markers of hypothalamic pituitary adrenal (HPA) axis activation and inflammation. Psychoneuroendocrinology. 2024 Nov;169:107145. doi: 10.1016/j.psyneuen.2024.107145. Epub 2024 Jul 24. |
| 34292344 | Result | Hantsoo L, Grillon C, Sammel M, Johnson R, Marks J, Epperson CN. Response to sertraline is associated with reduction in anxiety-potentiated startle in premenstrual dysphoric disorder. Psychopharmacology (Berl). 2021 Oct;238(10):2985-2997. doi: 10.1007/s00213-021-05916-6. Epub 2021 Jul 22. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Primary | Impact of Sertraline on ASR Magnitude | This outcome examines the impact of luteal phase treatment with a selective serotonin reuptake inhibitor (SSRI) (PMDD group only) on acoustic startle response (ASR). ASR is measured using the eyeblink reflex, measured by recording activity from the orbicularis oculi muscle. Recording is performed via two surface disk electrodes (Ag-AgCl) applied underneath the left eye; one in line with the pupil and one 1-2 cm lateral to the first one. Peak amplitude of the blink reflex is determined in the 20-120-ms time frame following stimulus onset. PMDD participants complete test day 3 (Luteal Month 3) while on sertraline and their ASR magnitude will be compared to their previous luteal test day (Luteal Month 2). ASR is measured in microvolts, and raw ASR results are standardized to t-scores. Higher ASR t-score indicates greater contraction of the the orbicularis oculi muscle. A t-score of 50 indicates the population mean with a standard deviation of 10. | 27 Controls and 23 PMDD (Sertraline) completed Luteal Month 2, and 24 Controls and 23 PMDD completed Luteal Month 3. Assessments were done on 1 day of the Luteal phase in Month 2 and 1 day of the Luteal phase in Month 3. | Posted | Mean | Standard Deviation | t score | Month 2 (Luteal), Month 3 (Luteal) |
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| Secondary | Interleukin 6 (IL-6) Level | Blood samples were collected to measure serum interleukin-6 (IL-6). IL-6 levels were compared in the follicular and luteal phases, between Control and PMDD groups. Levels are measured in picogram/milliliter (pg/mL). | 38 participants in the Control group and 32 participants in the PMDD group had blood available for IL-6 measurement in the Follicular phase. 36 Controls and 32 PMDD had blood available for IL-6 in the Luteal 1 phase. Assessments were done on 1 day of the Follicular phase and 1 day of the Luteal phase. | Posted | Mean | Standard Deviation | picogram/milliliter (pg/mL) | Month 1 (Follicular ), Month 2 (Luteal ) |
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| Secondary | Tumor Necrosis Factor Alpha (TNF-alpha) Level | Blood samples were collected to measure serum TNF-alpha levels in the Follicular and Luteal 1 phases. Levels are measured in picogram/milliliter (pg/mL). | 38 Controls and 32 PMDD had blood available to measure TNF-alpha in the Follicular phase. 36 Controls and 32 PMDD had blood available to measure TNF-alpha in the Luteal phase. Assessments were done on 1 day of the Follicular phase and 1 day of the Luteal phase. | Posted | Mean | Standard Deviation | pg/mL | Month 1 (Follicular ), Month 2 (Luteal ) |
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| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Sertraline | To determine the impact of short term luteal phase treatment with Sertraline 50mg tablets (PMDD group only) on arousal regulation across the menstrual cycle. Sertraline: Sertraline will be provided at a dose of 50 mg daily for up to 3 weeks, depending on the length of a woman's luteal phase. Medication will be taken only during the luteal phase. Women will initiate sertraline treatment upon determining that they have ovulated (using a urine LH Kit) and remain on sertraline until onset of their next menstrual period at which time they will stop taking the medication. | 0 | 23 | 0 | 23 | 0 | 23 |
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| D011084 |
| Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| Month 3 (Luteal) |
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