Allopregnanolone and Dynamic GABA-A Receptor Plasticity in Selective Serotonin Reuptake Inhibitor Responsive Premenstrual Dysphoric Disorder (BLOOM)

May 6, 2026 updated by: Johns Hopkins University
Premenstrual dysphoric disorder (PMDD) is a severe affective disorder impacting millions of women worldwide, thought to be due to altered sensitivity to hormone fluctuations across the menstrual cycle. Neuroactive steroid hormones (NAS) and the gamma-aminobutyric acid (GABA)-A receptor (GABAAR) are thought to play a role in PMDD. This research will assess the blood levels of GABAergic NAS, expression of associated enzymes, and expression of GABAAR subunits across the premenstrual (luteal) phase of the menstrual cycle in healthy controls and individuals with PMDD. Within the PMDD group, the investigators will assess how these measures are affected by a low-dose antidepressant medication versus placebo. The results will provide a comprehensive view of the changes in these systems across the menstrual cycle and will add to the investigator's understanding of the mechanisms that underlie PMDD, as well as therapeutic mechanisms of PMDD treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

288

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 Contact

  • Name: Victoria Paone, B.S.
  • Phone Number: 4436854258
  • Email: vpaone1@jh.edu

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Reproductive Mental Health Center
        • Principal Investigator:
          • Liisa Hantsoo, Ph.D.
        • Contact:
          • Victoria N Paone, B.S.
          • Phone Number: 443-685-4258
          • Email: vpaone1@jh.edu
        • Contact:
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jennifer Payne, MD

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

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • female sex,
  • fluent in the English language
  • regular menstrual cycles (24-35 days)
  • age 18-50 years old
  • ability to give written informed consent

Exclusion Criteria:

  • psychiatric medication use in the past 2 months
  • substance use disorder in the past 6 months
  • lifetime history of psychotic disorder including schizophrenia
  • schizoaffective disorder, major depression with psychotic features
  • history of psychiatric disorder other than PMDD in past year
  • active suicidal ideation with plan or attempt in past 6 months
  • steroid hormone or hormonal contraceptive use (except levonorgestrel as emergency contraceptive) in past 2 months
  • pregnancy in past 6 months
  • history of brain injury
  • current or history of endocrine disorder including uncontrolled diabetes or thyroid disease
  • BMI>40
  • History of arrythmias, severe liver impairment, history of seizure disorder
  • If currently taking the following meds: methylene blue, linezolid
  • Other prohibited concomitant meds are Monoamine oxidase inhibitors (MAOIs), pimozide, and disulfiram

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Participants delegated to the "control" arm will be individuals without premenstrual symptoms in the luteal phase of the menstrual cycle. Participants will be asked to track mood across the menstrual cycle, answer self-report surveys, and complete four blood draws.
Active Comparator: PMDD with sertraline
Participants delegated to the "PMDD with sertraline" arm will be individuals with severe premenstrual symptoms in the luteal phase of the menstrual cycle. Participants will be asked to track mood across two menstrual cycles, answer self-report surveys, and complete eight blood draws (four in each menstrual cycle). In the second cycle, participants in this arm will take a daily pill of 50 mg of sertraline from ovulation until menses onset (end of menstrual cycle 2).
Drug: sertraline 50 mg daily
The intervention will be in the form of an oral pill, taken daily, from the day of positive urine ovulation test result until the day of menses onset.
Placebo Comparator: PMDD with placebo
Participants delegated to the "PMDD with placebo" arm will be individuals with severe premenstrual symptoms in the luteal phase of the menstrual cycle. Participants will be asked to track mood across two menstrual cycles, answer self-report surveys, and complete eight blood draws (four in each menstrual cycle). In the second cycle, participants in this arm will take a daily placebo pill from ovulation until menses onset (end of menstrual cycle 2).
Drug: Placebo Oral Tablet
The placebo oral tablet will be of the same shape, color, and manufacturer as the sertraline 50 mg oral tablets. Tablet will be taken daily, from the day of positive urine ovulation test result until the day of menses onset.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuroactive Steroid Levels
Time Frame: Post ovulation up to 2 days, up to 5 days pre-menses prediction
The primary outcome variable is levels of neuroactive steroids in blood; from the early luteal phase (2 days post ovulation) compared to the late luteal phase (days 5 to 1 prior to predicted menses onset)
Post ovulation up to 2 days, up to 5 days pre-menses prediction

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurosteroidogenic enzyme expression levels
Time Frame: First menstrual cycle, up to 3 months
Neurosteroidogenic enzyme expression levels will be measured in the early luteal phase (2 days post ovulation) and the late luteal phase (days 5 to 1 prior to predicted menses onset). Levels will be compared between the healthy controls and PMDD groups at cycle 1, and between sertraline and placebo groups at cycle 2, respectively; between cycle 1 (first menstrual cycle when blood draws will be completed) and until the end of the participants' time on the study (2-3 months).
First menstrual cycle, up to 3 months
GABAAR subunit expression levels
Time Frame: first menstrual cycle, up to 3 months
GABAAR subunit expression will be measured in the early luteal phase (2 days post ovulation) and the late luteal phase (days 5 to 1 prior to predicted menses onset). The investigators will compare GABAAR subunit expression levels between controls and PMDD groups at L1, and between sertraline and placebo groups at L2, respectively; between cycle 1 (first menstrual cycle when blood draws will be completed) and until the end of the participants' time on the study (2-3 months)
first menstrual cycle, up to 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Liisa Hantsoo, PhD, Johns Hopkins University

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)

May 14, 2025

Primary Completion (Estimated)

July 1, 2029

Study Completion (Estimated)

July 1, 2029

Study Registration Dates

First Submitted

November 21, 2024

First Submitted That Met QC Criteria

November 21, 2024

First Posted (Actual)

November 26, 2024

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00445770
  • R01MH134904 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

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