Stress & Premenstrual Symptoms Study

Sponsor

Johns Hopkins University (Other)

Overall Status

Completed

CT.gov ID

NCT02777372

Collaborator

National Institute of Mental Health (NIMH) (NIH)

Enrollment

Location

Arm

Actual Duration (Months)

1.2

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

83 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

Actual Study Start Date :

Apr 1, 2016

Actual Primary Completion Date :

Dec 1, 2021

Actual Study Completion Date :

Dec 1, 2021

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 Names: Zoloft

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 Names:

Zoloft

Outcome Measures

Primary Outcome Measures

ASR magnitude based on menstrual cycle phase. [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).
Impact of Sertraline on ASR magnitude. [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

CRP (C-Reactive Protein) [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.
IL-6 (Interleukin 6) [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.
TNF-alpha (Tumor necrosis factor ALPHA) [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

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Participants must be:

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

Exclusion Criteria:

Participants cannot have:

Use of an psychotropic medication anytime in the past 2 months, per self-report
Drug or alcohol abuse history within previous 2 years
Lifetime history of psychotic disorder including, schizophrenia, schizoaffective disorder, major depression with psychotic features and bipolar disorder, per self-report
Currently homeless, per self-report
History of any Axis I disorder other then specific phobia within the past 12 months, per SCID interview
Active suicidal ideation (suicide plan or suicide attempt) within the previous 6 months, per self-report
Steroid hormone or hormonal contraceptive use in the past 6 months, per self-report, except emergency contraceptive use
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.
Sensitive hearing, per self-report.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Penn Center for Women's Behavioral Wellness, University of Pennsylvania School of Medicine	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

Johns Hopkins University
National Institute of Mental Health (NIMH)

Investigators

Principal Investigator: Liisa Hantsoo, PhD, Instructor

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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Publications

Responsible Party:

Johns Hopkins University

ClinicalTrials.gov Identifier:

NCT02777372

Other Study ID Numbers:

IRB00220794
1K23MH107831-01A1

First Posted:

May 19, 2016

Last Update Posted:

Dec 10, 2021

Last Verified:

Dec 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Keywords provided by Johns Hopkins University

Zoloft

PMS

Menses

Additional relevant MeSH terms:

Sertraline

Study Results

No Results Posted as of Dec 10, 2021