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

Johns Hopkins University

Status and phase: Enrolling; Phase 4

Conditions: Premenstrual Dysphoric Disorder (PMDD)

Treatments: Drug: sertraline 50 mg daily; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06704594

R01MH134904 (U.S. NIH Grant/Contract)

IRB00445770

Details and patient eligibility

About

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.

Enrollment: 288 estimated patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

288 participants in 3 patient groups, including a placebo group

Control

No Intervention group

Description:

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 group

Description:

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).

Treatment:

Drug: sertraline 50 mg daily

PMDD with placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo Oral Tablet