Clinical trial NCT02777372: Stress & Premenstrual Symptoms Study
Official title: Psychophysiology, Neurosteroids, and Stress in Premenstrual Dysphoric Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: PMDD
Stress
Mood
Keywords: Zoloft
premenstrual syndrome (PMS)
Menses
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2016-05-19
Enrollment: 84
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

Participants must be:

1. Aged 18 - 50 years, per self-report
2. Able to give written informed consent, per self-report
3. Fluent in written and spoken English
4. Have normal or corrected to normal hearing and vision, per self-report
5. Female participants must be experiencing regular menstrual cycles (24-39 days), per self-report
6. Have a negative urine drug screen.

Exclusion Criteria:

Participants cannot have:

1. Use of an psychotropic medication anytime in the past 2 months, per self-report
2. Drug or alcohol abuse history within previous 2 years
3. Lifetime history of psychotic disorder including, schizophrenia, schizoaffective disorder, major depression with psychotic features and bipolar disorder, per self-report
4. Currently homeless, per self-report
5. History of any Axis I disorder other then specific phobia within the past 12 months, per Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) interview
6. Active suicidal ideation (suicide plan or suicide attempt) within the previous 6 months, per self-report
7. Steroid hormone or hormonal contraceptive use in the past 6 months, per self-report, except emergency contraceptive use
8. Pregnancy in the past year, per self-report. Pregnancy during the study is also exclusionary. Participants must use a reliable, nonhormonal form of birth control during the study. If a participant becomes pregnant, she must inform study staff.
9. Sensitive hearing, per self-report.

Primary outcomes:
measure: Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase
timeFrame: Month 1 (Follicular), Month 2 (Luteal)
measure: Impact of Sertraline on ASR Magnitude
timeFrame: Month 2 (Luteal), Month 3 (Luteal)
Secondary outcomes:
measure: Interleukin 6 (IL-6) Level
timeFrame: Month 1 (Follicular ), Month 2 (Luteal )
measure: Tumor Necrosis Factor Alpha (TNF-alpha) Level
timeFrame: Month 1 (Follicular ), Month 2 (Luteal )
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Center for Women's Reproductive Mental Health, Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: Assistant Professor
name: Liisa Hantsoo, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.