Study on Allopregnanolone and Depression in Perimenopausal Women

• ClinicalTrials.gov Identifier: NCT05329779
• Recruitment Status: Recruiting
• First Posted: April 15, 2022
• Last Update Posted: November 10, 2022
• Sponsor: Brigham and Women's Hospital
• Information provided by (Responsible Party): Hadine Joffe, MD MSc, Brigham and Women's Hospital

Study Description

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.

Study Design

• 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

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

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

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

Contacts and Locations

Contacts

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

Locations

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

More Information

• 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
• Last Update Posted: November 10, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Pregnanolone; Brexanolone; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Neurosteroids; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents