Clinical trial NCT06238700: Study on Allopregnanolone and Depression in Women Across the Menopause Transition
Official title: Targeting Allopregnanolone to Probe Behavioral and Neurobiological Mechanisms That Underlie Depression in Women Across the Menopause Transition
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Depression
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2024-02-02
Enrollment: 80
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Within-person change in score on the Ruminative Responses Scale
timeFrame: Baseline to 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Hadine Joffe, MD MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Katherine Burdick, PhD
role: PRINCIPAL_INVESTIGATOR
References: