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

NCT06704594 | Recruiting Phase 4 DMC

• 2 other identifiers: IRB00445770R01MH134904
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 2

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.

Conditions

Premenstrual Dysphoric Disorder (PMDD)

Keywords

pmdd; premenstrual dysphoric disorder; pms; premenstrual symptoms; premenstrual syndrome; blood draw; sertraline; ssri; mood symptoms; women; women with pms; women with pmdd; luteal phase; follicular phase; womens reproductive mental health; womens health; womens reproductive health; menstrual cycle; menses; periods; allopregnanolone; neuroactive steroids; inflammatory markers; epigenetics

Outcome Measures

Primary Outcomes (1)

• Neuroactive Steroid Levels

  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 Outcomes (2)

• Neurosteroidogenic enzyme expression levels

  First menstrual cycle, up to 3 months

• GABAAR subunit expression levels

  first menstrual cycle, up to 3 months

Study Arms (3)

Control

NO INTERVENTION

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.

PMDD with sertraline

ACTIVE COMPARATOR

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

PMDD with placebo

PLACEBO COMPARATOR

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

Interventions

sertraline 50 mg daily DRUG

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.

PMDD with sertraline

Placebo Oral Tablet DRUG

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.

PMDD with placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Reproductive Mental Health Center

Baltimore, Maryland, 21205, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Conditions

Premenstrual Dysphoric Disorder; Premenstrual Syndrome

Interventions

Sertraline

Condition Hierarchy (Ancestors)

Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Liisa Hantsoo, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Victoria Paone, B.S.

CONTACT

4436854258; vpaone1@jh.edu

Victoria Seo, B.S.

CONTACT

vseo1@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: November 26, 2024
• Study Start: May 14, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)