Study on Allopregnanolone and Depression in Perimenopausal Women

Mass General Brigham

Status and phase: Terminated; Phase 4

Conditions: Depression

Treatments: Drug: placebo; Drug: brexanolone

Study type: Interventional

Funder types: Other

Identifiers

NCT05329779

2021P003137

Details and patient eligibility

About

This study aims to identify how the progesterone metabolite allopregnanolone affects behavior and neurobiology that may underlie perimenopausal depression.

Full description

Midlife women are burdened with depression risk that is at least partly attributed to changing reproductive steroid dynamics across a prolonged reproductive transition. The investigators hypothesize that declining endogenous allopregnanolone (ALLO) levels across the menopause transition underlies perimenopausal depression. This mechanistic trial aims to amplify the contrast between lower endogenous ALLO levels in perimenopausal women and higher levels experimentally induced by exogenous ALLO. This will be achieved by using the exogenous ALLO treatment, brexanolone, which is FDA-approved to treat depression in postpartum patients, in a randomized, double-blind, parallel-arm, placebo-controlled trial. By manipulating ALLO levels together with key measurement of depression domains, this study harnesses the endocrine biology of perimenopause to explicate behavioral and neurobiological mechanisms underlying depression in perimenopausal women.

Enrollment: 2 patients

Sex: Female

Ages: 40 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Healthy perimenopausal women ages 40 to 60 years
• Depressive symptoms
• Able to read Arabic numerals and perform simple arithmetic
• Able to provide written informed consent

Exclusion criteria

• Use of medications to treat depression
• Systemic hormone therapy
• Contraindicated medications with brexanolone
• Other psychiatric illnesses that are considered to be primary
• Current suicidal ideation
• Active substance use disorders
• Unstable medical conditions
• Obstructive sleep apnea or other primary sleep disorders
• Abnormal hepatic and renal function
• Known allergy to progesterone, exogenous allopregnanolone, or brexanolone
• History of head injury resulting in loss of consciousness > 20 min
• Inability to comply with barrier contraceptive methods
• Known intellectual disability
• Investigator judgement that study participation constitutes substantial risk given medical or psychiatric condition
• Current or recent participation in clinical trial expected to interfere with risk of or interpretation of study data
• Inability to comply with study procedures

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2 participants in 2 patient groups, including a placebo group

brexanolone

Experimental group

Description:

Participants will receive a continuous 60-hr intravenous infusion of brexanolone

Treatment:

Drug: brexanolone

placebo

Placebo Comparator group

Description:

Participants will receive a continuous 60-hr infusion of placebo

Treatment:

Drug: placebo