Stress & Premenstrual Symptoms Study

• ClinicalTrials.gov Identifier: NCT02777372
• Recruitment Status: Recruiting
• First Posted: May 19, 2016
• Last Update Posted: January 15, 2021
• Sponsor: Johns Hopkins University
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

This is a pilot 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 male and 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, cortisol, and immune markers, as well as hormone and genetic measures. 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 PMDD (premenstrual mood dysphoric disorder), 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 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. CRF-enhanced startle is mediated by the bed nucleus of the stria terminalis (BNST). Thus, ALLO appears to impact the BNST and anxiety, versus the amygdala and acute fear. The proposed study will examine both anticipatory anxiety and cued fear at baseline and with SSRI treatment. The magnitude of the ASR with the former manipulation would reflect BNST activity which we hypothesize is dysregulated in women with PMDD. Secondary aims are to examine the impact of luteal phase treatment with a selective serotonin reuptake inhibitor (SSRI) on psychophysiology in women with PMDs and to examine the relationship between affective symptoms, stress regulation and immune function among these women, as well as associations with hormone levels and genetic markers.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 127 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Acoustic Startle Response in Women With Premenstrual Mood Disorders
• Study Start Date: January 2016
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

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 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

Outcome Measures

Primary Outcome Measures :

1. ASR magnitude based on menstrual cycle phase. [ Time Frame: Baseline (day 1) and ends at 3 months ]
   During the luteal phase vs the follicular phase of the menstrual cycle in women with PMDs, compared to luteal and follicular ASR in healthy female controls. The startle response will be measured using the eyeblink reflex, measured by recording activity from the orbicularis oculi muscle. Recording will be 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 will be determined in the 20-120-ms time frame following stimulus onset relative to baseline (baseline is the average baseline EMG level for the 50 ms immediately preceding auditory stimulus onset).
2. Impact of Sertraline on ASR magnitude. [ Time Frame: During luteal phase of menstrual cycle during test day 3 ]
   To determine the impact of luteal phase treatment with an SSRI (PMD group only) on arousal regulation across the menstrual cycle. The startle response will be measured using the eyeblink reflex, measured by recording activity from the orbicularis oculi muscle. Recording will be 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 will be determined in the 20-120-ms time frame following stimulus onset relative to baseline (baseline is the average baseline EMG level for the 50 ms immediately preceding auditory stimulus onset). Participants will return for test day 3 while on Sertraline and their ASR magnitude will be compared to their previous test days.

Secondary Outcome Measures :

1. CRP (C-Reactive Protein) [ Time Frame: Baseline (day 1) and ends at 3 months ]
   As there is an intimate relationship between HPA axis function, psychophysiology and psychoneuroimmunology, the investigators will collect blood samples to measure CRP (C-Reactive Protein) before and after the acoustic startle paradigm.
2. IL-6 (Interleukin 6) [ Time Frame: Baseline (day 1) and ends at 3 months ]
   As there is an intimate relationship between HPA axis function, psychophysiology and psychoneuroimmunology, the investigators will collect blood samples to measure IL-6 (Interleukin 6) before and after the acoustic startle paradigm.
3. TNF-alpha (Tumor necrosis factor ALPHA) [ Time Frame: Baseline (day 1) and ends at 3 months ]
   As there is an intimate relationship between HPA axis function, psychophysiology and psychoneuroimmunology, the investigators will collect blood samples to measure TNF-alpha (Tumor necrosis factor ALPHA) before and after the acoustic startle paradigm.

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 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

Contacts

Contact: Joanna Marks; 215-746-1157; marksjoa@mail.med.upenn.edu

Contact: Liisa Hantsoo, PhD; 215-746-1156; liisaha2@mail.med.upenn.edu

Locations

United States, Pennsylvania

Penn Center for Women's Behavioral Wellness, University of Pennsylvania School of Medicine; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Joanna Marks, B.A. 215-746-1157 marksjoa@mail.med.upenn.edu

Contact: Liisa Hantsoo, PhD 215-746-1156 LiisaHa2@mail.med.upenn.edu

Principal Investigator: Liisa Hantsoo, PhD

Sponsors and Collaborators

Johns Hopkins University

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Liisa Hantsoo, PhD; Instructor

More Information

Additional Information:

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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. 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. Review.

• 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
• Last Update Posted: January 15, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Johns Hopkins University:

Zoloft; 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