Stress & Premenstrual Symptoms Study

• ClinicalTrials.gov Identifier: NCT02777372
• Recruitment Status: Completed
• First Posted: May 19, 2016
• Results First Posted: November 17, 2022
• Last Update Posted: November 17, 2022
• Sponsor: Johns Hopkins University
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
PMDD; Stress; Mood	Drug: Sertraline	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Psychophysiology, Neurosteroids, and Stress in Premenstrual Dysphoric Disorder
• Actual Study Start Date: April 1, 2016
• Actual Primary Completion Date: December 1, 2021
• Actual Study Completion Date: December 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sertraline; 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.	Drug: 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.; Other Name: Zoloft
No Intervention: Control; No intervention.

Outcome Measures

Primary Outcome Measures :

1. Acoustic Startle Response (ASR) Magnitude Based on Menstrual Cycle Phase [ Time Frame: Month 1 (Follicular), Month 2 (Luteal) ]
   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.
2. Impact of Sertraline on ASR Magnitude [ Time Frame: Month 2 (Luteal), Month 3 (Luteal) ]
   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.

Secondary Outcome Measures :

1. Interleukin 6 (IL-6) Level [ Time Frame: Month 1 (Follicular ), Month 2 (Luteal ) ]
   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).
2. Tumor Necrosis Factor Alpha (TNF-alpha) Level [ Time Frame: Month 1 (Follicular ), Month 2 (Luteal ) ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Maryland

Center for Women's Reproductive Mental Health, Johns Hopkins University School of Medicine

Baltimore, Maryland, United States, 21205

Sponsors and Collaborators

Johns Hopkins University

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Liisa Hantsoo, PhD; Assistant Professor

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol and Statistical Analysis Plan  [PDF] February 1, 2022

More Information

Additional Information:

Johns Hopkins Center for Women's Reproductive Mental Health 

Publications:

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.

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.

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.

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.

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.

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.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02777372
• Other Study ID Numbers: IRB00220794; 1K23MH107831-01A1 ( U.S. NIH Grant/Contract )
• First Posted: May 19, 2016
• Results First Posted: November 17, 2022
• Last Update Posted: November 17, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Johns Hopkins University:

Zoloft; premenstrual syndrome (PMS); Menses

Additional relevant MeSH terms:

Sertraline; Antidepressive Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs