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

Phase 4

Recruiting

• Conditions: Premenstrual Dysphoric Disorder (PMDD)
• Interventions: Drug: sertraline 50 mg daily; Drug: Placebo Oral Tablet

• Registration Number: NCT06704594
• Lead Sponsor: Johns Hopkins University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-21
• Study First Submitted QC: 2024-11-21
• Study First Posted: 2024-11-26
• Study Start: 2025-04-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-14
• Primary Completion: 2029-07-01
• Study Completion: 2029-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 288

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PMDD with sertraline	sertraline 50 mg daily	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).
PMDD with placebo	Placebo Oral Tablet	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).

Primary Outcome Measures

Name	Time	Method
Neuroactive Steroid Levels	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)

Secondary Outcome Measures

Name	Time	Method
Neurosteroidogenic enzyme expression levels	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).
GABAAR subunit expression levels	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)

Trial Locations

Locations (2)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Reproductive Mental Health Center; 🇺🇸 Baltimore, Maryland, United States