Study on Allopregnanolone and Depression in Perimenopausal Women

NCT ID: NCT05329779

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-04
• Study Completion Date: 2023-07-18

Brief Summary

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

Detailed 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.

Conditions

Depression

Study Design

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

Study Groups

brexanolone

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

Group Type: EXPERIMENTAL

brexanolone

Intervention Type: DRUG

Brexanolone is a derivative of allopregnanolone, which is FDA-approved to treat postpartum depression.

placebo

Participants will receive a continuous 60-hr infusion of placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

The placebo is a 0.45% sodium chloride infusion.

Interventions

brexanolone

Brexanolone is a derivative of allopregnanolone, which is FDA-approved to treat postpartum depression.

Intervention Type: DRUG

placebo

The placebo is a 0.45% sodium chloride infusion.

Intervention Type: DRUG

Other Intervention Names

Zulresso; allopregnanolone

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hadine Joffe, MD MSc

Study Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2021P003137

Identifier Type: -

Identifier Source: org_study_id