Clinical trial NCT06704594: Allopregnanolone and Dynamic GABA-A Receptor Plasticity in Selective Serotonin Reuptake Inhibitor Responsive Premenstrual Dysphoric Disorder
Official title: Allopregnanolone and Dynamic GABA-A Receptor Plasticity in Selective Serotonin Reuptake Inhibitor Responsive Premenstrual Dysphoric Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
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
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2024-11-26
Enrollment: 288
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Neuroactive Steroid Levels
timeFrame: Post ovulation up to 2 days, up to 5 days pre-menses prediction
Secondary outcomes:
measure: Neurosteroidogenic enzyme expression levels
timeFrame: First menstrual cycle, up to 3 months
measure: GABAAR subunit expression levels
timeFrame: first menstrual cycle, up to 3 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Reproductive Mental Health Center
state: Maryland
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Johns Hopkins University
name: Liisa Hantsoo, PhD
role: PRINCIPAL_INVESTIGATOR
References: