Study on Allopregnanolone and Depression in Women Across the Menopause Transition

Not Applicable

Recruiting

• Conditions: Depression
• Interventions: Other: placebo; Dietary Supplement: pregnenolone

• Registration Number: NCT06238700
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

This study aims to identify how enhanced allopregnanolone activity (via pregnenolone) 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. We 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 induced by pregnenolone. This will be achieved by using the over-the-counter dietary supplement, pregnenolone, 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 women across the menopause transition.

Study Timeline

• Study First Submitted: 2024-01-26
• Study First Submitted QC: 2024-01-26
• Study First Posted: 2024-02-02
• Study Start: 2024-05-14
• Status Verified: 2024-07
• Last Update Submitted: 2024-11-13
• Last Update Posted: 2024-11-15
• Primary Completion: 2027-07-31
• Study Completion: 2027-08-31

Recruitment & Eligibility

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

Inclusion Criteria

• Healthy women ages 40 to 60 years in the menopause transition
• Depressive symptoms
• Psychotropic medications are allowed if the dose is stable prior to screening and throughout the study
• Able to read Arabic numerals and perform simple arithmetic
• Able to provide written informed consent

Exclusion Criteria

• Systemic hormone therapy
• Contraindicated medications with pregnenolone
• Systemic corticosteroid
• 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 pregnenolone
• 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 take placebo twice per day for four weeks
pregnenolone	pregnenolone	Participants will take 250mg of pregnenolone twice per day (daily total=500mg) for four weeks

Primary Outcome Measures

Name	Time	Method
Within-person change in score on the Ruminative Responses Scale	Baseline to 2 weeks	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