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CompletedNCT00678574Updated Jul 27, 2018Results posted

The Role of GABA and Neurosteroids in Premenstrual Dysphoric Disorder

A Phase 4 interventional study of fluoxetine in Premenstrual Dysphoric Disorder and Premenstrual Syndrome, sponsored by University of Pennsylvania. Completed at 1 site in United States. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-07-27.

Sponsored by University of Pennsylvania · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
45
Allocation
Non-randomized
Ages
18 Years to 45 Years
Sex
Female
01

Study summary

The purpose of the study proposed is to investigate the role of neurosteroids and GABA in the pathophysiology and treatment of premenstrual dysphoric disorder (PMDD) by 1) measuring cortical gama-aminobutyric acid levels (GABA levels) using nuclear magnetic resonance spectroscopy (MRS) during the follicular and mid-luteal phases of the menstrual cycle pre and post treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac®, Sarafem®), and 2) correlating cerebrospinal fluid (CSF) and plasma GABA and neurosteroid levels with cortical GABA levels at these same time points. Neurosteroids to be measured include allopregnanolone, pregnenolone, and pregnenolone sulfate. Findings from women with PMDD will be compared to those of healthy subjects.

02

Conditions studied

  • Premenstrual Dysphoric Disorder
  • Premenstrual Syndrome

Keywords

  • hormones
  • menses
  • PMS
  • PMDD
03

In context

Premenstrual Syndrome

177 studies on the registry are indexed under Premenstrual Syndrome; 30 are open to participants now.

This study's enrollment of 45 is below the median of 70 across 153 interventional studies indexed under Premenstrual Syndrome.

Browse Premenstrual Syndrome studies →

Lead sponsor

University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • Aged 18 - 45 years old and able to give voluntary written informed consent.
  • Willing to complete a daily log of mood symptoms for 7 consecutive menstrual cycles: two menstrual cycles during the Screening Phase (Phase 1), one menstrual cycle during the Testing Phase (Phase 2), and four menstrual cycles during the Medication Treatment Phase and Post-Treatment Phase (Phase 3). All subjects who successfully complete Phases 1 and 2, and the Medication Treatment Phase, will be invited to participate in Phase 3 approximately three months later. Phase 3 will involve repeating all procedures conducted in Phase 2, including the daily log of mood symptoms.
  • Meet DSM-IV criteria for premenstrual dysphoric disorder, confirmed by the Daily Record of Severity of Problems (DRSP; Endicott \& Harrison) for 2 consecutive menstrual cycles (Phase 1). The DRSP is a self-rated symptom checklist, which requires individuals to rate their symptoms of PMDD according to the DSM-IV research criteria scale on a scale from 1 (symptom not present) to 6 (symptom extreme). During the last 7 days of the menstrual cycle compared to days 5-11, patients must have a 30% increase in their average (over 2 menstrual cycles) score for 5 of these 10 symptoms. Symptoms must be "not present" or "minimal" during the postmenstrual week.
  • Average 19-item Hamilton Depression Rating Scale (HAM-D) scores \< 5 during the follicular phase and > 16 during the luteal phase.
  • Have regular menstrual cycles 28 to 32 days in length. Each of the screening cycles must be ovulatory as confirmed by plasma progesterone levels of >5 ng/ml during the luteal phase.

Exclusion criteria

Exclusion Criteria:

  • Presence of any other comorbid DSM-IV Axis I disorder.
  • Meeting DSM-IV criteria for psychoactive substance (excluding nicotine) dependence within the preceding 4 months.
  • A history of serious medical or neurological illness, including (but not limited to) major cardiovascular disease, severe hypertension, intracranial mass lesions, seizure disorder, severe hepatic or renal disease, unstable endocrine or metabolic disease, and unstable hematologic disease.
  • Use of anticonvulsant or benzodiazepines within the last month.
  • Use of psychotropic medication in last week (except as stated above).
  • Use of steroid contraceptives within the previous 4 months, including birth control pill, birth control patch, birth control ring, and Depo-Provera®. Subjects will be asked to use abstinence or the barrier method (condoms) as forms of contraception in this study.
  • Alcohol consumption greater than 7 drinks/week.
  • Current pregnancy.
  • Metallic implants.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
45 participants (actual)

Study arms

  • Experimental
    Premenstrual Dysphoric Disorder (PMDD) group

    PMDD group received fluoxetine 20 mg daily by mouth for 2-3 months

    Drug: fluoxetine

  • No intervention
    Healthy controls

Interventions

  • Drugfluoxetine

    Fluoxetine 20 mg daily by mouth for 2-3 months.

    Also known as: Prozac, Sarafem

06

What researchers measure

Primary outcomes

  1. Change in Cortical Gama-aminobutyric Acid Levels (GABA Levels) Pre and Post SSRI Treatment

    GABA levels would be assessed during the follicular and mid-luteal phases of the menstrual cycle pre and post treatment with the SSRI.

    Time frame: 2-3 months post-treatment w/ fluoxetine.

07

Results

Posted Jul 17, 2017
Limitations and caveats
Data from this study has not yet been analyzed nor peer reviewed. As much information as possible was entered into the results section of this trial, however information is missing as it pertains to specific measurements collected.

Participant flow

45 subjects were recruited at an outpatient practice at Yale University, CT.

Participant flow — Overall Study
MilestonePMDDHealthy Controls
Started1827
Completed1827
Not completed00

Outcome measures

PrimaryChange in Cortical Gama-aminobutyric Acid Levels (GABA Levels) Pre and Post SSRI Treatment

GABA levels would be assessed during the follicular and mid-luteal phases of the menstrual cycle pre and post treatment with the SSRI.

Time frame:
2-3 months post-treatment w/ fluoxetine.

No measurements were reported for this outcome.

Adverse events

Collected over Adverse event data was collected throughout the course of the study.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Fluoxetine0/18 (0%)0/18 (0%)0/18 (0%)
No Treatment0/27 (0%)0/27 (0%)0/27 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)PMDD GroupHealthy ControlsTotal
<=18 years000
Between 18 and 65 years182745
>=65 years000
Sex: Female, Male
Sex: Female, Male(Participants)PMDD GroupHealthy ControlsTotal
Female182745
Male000
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)PMDD GroupHealthy ControlsTotal
Count of participants——0
08

Study locations

1 site
  • Yale University
    New Haven, Connecticut 06511, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 27, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00678574
Lead sponsor
University of Pennsylvania
Collaborators
National Institute of Mental Health (NIMH)
Responsible party
Sponsor
First posted
May 15, 2008
Start date
Mar 1998
Primary completion
Dec 2008
Completion
Dec 2008
Results posted
Jul 17, 2017
Last update
Jul 27, 2018

Study contacts

Cynthia N Epperson, MD
principal investigator · University of Pennsylvania School of Medicine Department of Psychiatry

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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