- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02777372
Stress & Premenstrual Symptoms Study
October 25, 2022 updated by: Johns Hopkins University
Psychophysiology, Neurosteroids, and Stress in Premenstrual Dysphoric Disorder
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.
Study Overview
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 Type
Interventional
Enrollment (Actual)
84
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21205
- Center for Women's Reproductive Mental Health, Johns Hopkins University School of Medicine
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 50 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
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 Structured Clinical Interview for Diagnostic and Statistical Manual (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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Control
No intervention.
|
|
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.
|
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Month 1 (Follicular), Month 2 (Luteal)
|
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.
|
Month 2 (Luteal), Month 3 (Luteal)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
Month 1 (Follicular ), Month 2 (Luteal )
|
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).
|
Month 1 (Follicular ), Month 2 (Luteal )
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Liisa Hantsoo, PhD, Assistant Professor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2016
Primary Completion (Actual)
December 1, 2021
Study Completion (Actual)
December 1, 2021
Study Registration Dates
First Submitted
April 19, 2016
First Submitted That Met QC Criteria
May 16, 2016
First Posted (Estimate)
May 19, 2016
Study Record Updates
Last Update Posted (Actual)
November 17, 2022
Last Update Submitted That Met QC Criteria
October 25, 2022
Last Verified
October 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB00220794
- 1K23MH107831-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Stress
-
Massachusetts General HospitalCompletedStress | Emotional Stress | Psychological Stress | Social Stress | Life StressUnited States
-
University of PadovaRecruitingStress | Stress Disorder | Work Related StressItaly
-
University of California, Los AngelesUniversity of California, San Francisco; Stanford University; California Initiative...Enrolling by invitationStress | Stress, Psychological | Stress, Emotional | Stress, Physiological | Stress ReactionUnited States
-
Duquesne UniversityUniversity of California, San Diego; West Penn Allegheny Health System; El Centro... and other collaboratorsTerminated
-
University of Sao PauloCompleted
-
Dana-Farber Cancer InstituteEnrolling by invitationStress | Post Traumatic Stress Disorder | Work Related StressUnited States
-
Syracuse VA Medical CenterUS Department of Veterans AffairsCompletedEmotional Stress | Psychological Stress | Life StressUnited States
-
Royal Cornwall Hospitals TrustEnrolling by invitationStress | Stress, Psychological | Stress, JobUnited Kingdom
-
Taichung Veterans General HospitalUnknown
-
Northumbria UniversityVolac International LtdNot yet recruitingStress | Mood | Physiological Stress
Clinical Trials on Sertraline
-
Beijing HuiLongGuan HospitalCompleted
-
Maastricht University Medical CenterPfizerCompletedDepression | Chest Pain | Panic AttacksNetherlands
-
Pfizer's Upjohn has merged with Mylan to form Viatris...Completed
-
University of Sao PauloCompletedObsessive-Compulsive DisorderBrazil
-
Washington University School of MedicineNational Heart, Lung, and Blood Institute (NHLBI)CompletedDepression | Myocardial Infarction | Heart Diseases | Cardiovascular Diseases | Angina, UnstableUnited States
-
TakedaCompletedCrohn's Disease | Ulcerative ColitisBelgium, United States, Korea, Republic of, Malaysia, Canada, Israel, Australia, Hungary, Czechia, Germany
-
University of PittsburghCompleted
-
Su RuiUnknown
-
Rhode Island HospitalStanford University; University of Cincinnati; American Epilepsy Society; Epilepsy...CompletedDepression | Stress Disorders, Post-Traumatic | Dissociative Disorders | Conversion Disorder | Convulsion, Non-EpilepticUnited States
-
TakedaCompleted