Recruiting

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

Sponsor:

Johns Hopkins University

Code:

NCT06704594

Conditions

Premenstrual Dysphoric Disorder (PMDD)

Eligibility Criteria

Sex: Female

Age: 18 - 50

Healthy Volunteers: Accepted

Interventions

sertraline 50 mg daily

Placebo Oral Tablet

Study Details

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)

Study ID

NCT06704594

Start date

May 14, 2025

Status verified date

May, 2026

Completion date

Jul 1, 2029

Anticipated

Primary completion date

Jul 1, 2029

Anticipated

Eligibility Criteria

Sex: Female

Age: 18 - 50

Healthy Volunteers: Accepted

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

Enrollment

288 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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).

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).

Interventions

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 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.

Primary outcome measure

Neuroactive Steroid Levels [ Time Frame: Post ovulation up to 2 days, up to 5 days pre-menses prediction ]

Central Contacts and Locations

Central contacts

Victoria Paone, B.S.

4436854258 vpaone1@jh.edu

Victoria Seo, B.S.

vseo1@jh.edu

Locations

Reproductive Mental Health Center

Recruiting

Baltimore, Maryland, United States, 21205

Contacts

Victoria N Paone, B.S.

443-685-4258 vpaone1@jh.edu

Liisa Hantsoo, Ph.D.

lhantso1@jhmi.edu

Principal Investigator:

Liisa Hantsoo, Ph.D.

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22903

Contacts

Lauren A Williamson, PhD

434-297-4689 LEA6D@uvahealth.org

Emmalee N Johnson, B.A.

enj8tnz@uvahealth.org

Principal Investigator:

Jennifer Payne, MD

More Information

Sponsor

Johns Hopkins University

Last update posted

May 7, 2026

Last verified

May, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-05-07.