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Study on Allopregnanolone and Depression in Perimenopausal Women

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ClinicalTrials.gov Identifier: NCT05329779
Recruitment Status : Recruiting
First Posted : April 15, 2022
Last Update Posted : November 10, 2022
Information provided by (Responsible Party):
Hadine Joffe, MD MSc, 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.

Condition or disease Intervention/treatment Phase
Depression Drug: brexanolone Drug: placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Using Allopregnanolone to Probe Behavioral and Neurobiological Mechanisms That Underlie Depression in Women During the Perimenopause
Actual Study Start Date : November 4, 2022
Estimated Primary Completion Date : April 1, 2026
Estimated Study Completion Date : May 1, 2026

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: brexanolone
Participants will receive a continuous 60-hr intravenous infusion of brexanolone
Drug: brexanolone
Brexanolone is a derivative of allopregnanolone, which is FDA-approved to treat postpartum depression.
Other Names:
  • Zulresso
  • allopregnanolone

Placebo Comparator: placebo
Participants will receive a continuous 60-hr infusion of placebo
Drug: placebo
The placebo is a 0.45% sodium chloride infusion.

Primary Outcome Measures :
  1. Within-person change in score on the Ruminative Responses Scale [ Time Frame: 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05329779

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Contact: Aleta Wiley, MPH MSc 617-525-9627 awiley1@bwh.harvard.edu

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United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Aleta Wiley         
Sponsors and Collaborators
Brigham and Women's Hospital
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Responsible Party: Hadine Joffe, MD MSc, Study Principal Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT05329779    
Other Study ID Numbers: 2021P003137
First Posted: April 15, 2022    Key Record Dates
Last Update Posted: November 10, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Central Nervous System Depressants
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
GABA Agents