Study on Allopregnanolone and Depression in Perimenopausal Women

Phase 4

Recruiting

• Conditions: Depression
• Interventions: Drug: placebo; Drug: brexanolone

• Registration Number: NCT05329779
• Lead Sponsor: Brigham and Women's Hospital

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.

Study Timeline

• Study First Submitted: 2022-04-08
• Study First Submitted QC: 2022-04-08
• Study First Posted: 2022-04-15
• Status Verified: 2022-11
• Study Start: 2022-11-04
• Last Update Submitted: 2022-11-08
• Last Update Posted: 2022-11-10
• Primary Completion: 2026-04-01
• Study Completion: 2026-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	Participants will receive a continuous 60-hr infusion of placebo
brexanolone	brexanolone	Participants will receive a continuous 60-hr intravenous infusion of brexanolone

Primary Outcome Measures

Name	Time	Method
Within-person change in score on the Ruminative Responses Scale	Baseline to 4 days	The Ruminative Responses Scale (RRS) comprises 22 items which ask how frequently the participant thinks certain statements when they feel depressed. Each item is scored from 1-4. Total scores range from 22-88 with higher scores indicating more severe rumination.

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States