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

NCT ID: NCT06704594

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 288 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-14
• Study Completion Date: 2029-07-01

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 Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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).

Group Type: ACTIVE_COMPARATOR

sertraline 50 mg daily

Intervention Type: 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 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).

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: 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.

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Liisa Hantsoo, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Reproductive Mental Health Center

Baltimore, Maryland, United States

Site Status: RECRUITING

University of Virginia

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Liisa Hantsoo, Doctor of Philosophy, PhD

Role: CONTACT

lhantso1@jhmi.edu

215-645-7035

Victoria Paone, B.S.

Role: CONTACT

vpaone1@jh.edu

4436854258

Facility Contacts

Victoria N Paone, B.S.

Role: primary

vpaone1@jh.edu

443-685-4258

Liisa Hantsoo, Ph.D.

Role: backup

lhantso1@jhmi.edu

Lauren A Williamson, PhD

Role: primary

LEA6D@uvahealth.org

434-297-4689

Emmalee N Johnson, B.A.

Role: backup

enj8tnz@uvahealth.org

Other Identifiers

R01MH134904

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00445770

Identifier Type: -

Identifier Source: org_study_id