Alcohol Use Disorder (AUD), Major Depressive Disorder (MDD)
Conditions
Keywords
Pregnenolone, Alcohol Use Disorder, Major Depressive Disorder, Neurosteroids, fMRI, Anxiety, Substance Use Disorders
Brief summary
This study will evaluate whether pregnenolone is an effective treatment for adults with Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD). Participants will be randomly assigned to receive either pregnenolone or placebo for 12 weeks in a double-blind study. Researchers will assess alcohol consumption, alcohol craving, depressive symptoms, and anxiety symptoms throughout treatment. The study will also use magnetic resonance imaging (MRI) to examine how pregnenolone affects brain circuits involved in addiction and mood regulation. The goal is to determine whether pregnenolone can improve both alcohol-related and mood-related outcomes and to identify the neural mechanisms associated with treatment response.
Detailed description
Alcohol Use Disorder (AUD) commonly co-occurs with Major Depressive Disorder (MDD), resulting in substantial morbidity and limited treatment success. Pregnenolone is an endogenous neurosteroid that has demonstrated potential therapeutic effects on alcohol use, craving, mood symptoms, and neural pathways implicated in addiction and depression. This randomized, double-blind, placebo-controlled trial will enroll approximately 100 adults aged 21 to 55 years with DSM-5 diagnoses of AUD and MDD. Participants will be randomized to receive pregnenolone 500 mg/day (250 mg twice daily) or matched placebo for 12 weeks. The primary objective is to determine whether pregnenolone reduces alcohol consumption compared with placebo. Secondary clinical objectives include evaluating effects on alcohol craving, depressive symptom severity, and anxiety symptoms. Mechanistic objectives include examining the effects of pregnenolone on resting-state functional connectivity between the amygdala and prefrontal cortex and on brain responses to alcohol-related cues using functional magnetic resonance imaging (fMRI). Clinical assessments will be conducted throughout the treatment period, and MRI scans will be obtained at baseline and Week 12. Relationships between neuroimaging measures and clinical outcomes will also be evaluated. Findings from this study may support the development of a novel treatment approach for individuals with co-occurring AUD and MDD.
Interventions
DRUGPregnenolone
Pregnenolone 500 mg/day administered as 250 mg twice daily for 12 weeks.
DRUGPlacebo
Matching placebo capsules administered twice daily for 12 weeks.
Sponsors
Sherwood Brown, MD, PhD
The University of Texas at Dallas
Duke University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a randomized, double-blind, placebo-controlled trial. Participants, investigators, and care providers will remain blinded to treatment assignment throughout the study.
Intervention model description
Participants will be randomized in a parallel-group design to receive either pregnenolone 500 mg/day or matching placebo for 12 weeks.
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Age 21 to 55 years. * Meets DSM-5 criteria for Alcohol Use Disorder (AUD). * Meets DSM-5 criteria for Major Depressive Disorder (MDD). * Able to provide informed consent. * Willing and able to comply with study procedures and assessments
Exclusion criteria
* Current diagnosis of bipolar disorder, schizophrenia spectrum disorder, or other psychotic disorder. * Current substance use disorder requiring immediate treatment other than alcohol or nicotine. * Significant unstable medical or neurologic illness that would interfere with participation or study assessments. * Contraindications to magnetic resonance imaging (MRI). * Current pregnancy or breastfeeding. * Current use of medications or treatments that would interfere with study participation or interpretation of results. * Significant suicide risk requiring a higher level of care. * Any condition that, in the investigator's judgment, would make participation unsafe or compromise study integrity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Consumption | Baseline to Week 12 | Change in alcohol consumption from baseline to Week 12. The timeline follow-back (TLFB) is a semi-structured interview method assessing recent drinking in which participants retrospectively estimate daily quantity of alcohol consumption during specified time periods. The TLFB will be used to assess alcohol use including drinks/drinking day and drinks/day (7-day average). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Craving | Baseline to Week 12 | Change in alcohol craving severity from baseline to Week 12. The PACS is a 5-item, self-report measure that includes questions about the frequency, intensity and duration of alcohol craving in the previous week. PACS will be used to measure alcohol craving. |
| Depressive Symptom Severity | Baseline to Week 12 | Change in depressive symptom severity from baseline to Week 12. The Quick Inventory of Depressive Symptomatology Clinician version (QIDS-C) is a 16-item observer-rated scale assessing depressive symptom severity. The QIDS-C will be used to measure changes in depressive symptom severity. |
| Anxiety Symptom Severity | Baseline to Week 12 | Change in anxiety symptom severity from baseline to Week 12. The Hamilton Anxiety Rating Scale (HAM-A) is a 14-item, observer-rated scale assessing anxiety symptom severity. The HAM-A will be used to measure changes in anxiety symptom severity. |
| Amygdala-Prefrontal Functional Connectivity | Baseline and Week 12 | Change in resting-state functional connectivity between the amygdala and prefrontal cortex. Resting-state functional connectivity (rsFC) will be measured. Each participant's average connectivity between prefrontal cortex and amygdala regions of interest (ROIs) will be calculated by averaging the Fisher's Z-transformed pairwise correlation coefficients among the selected ROI pairs. |
Countries
United States
Contacts
CONTACTE. Sherwood Brown
CONTACTFrancesca Filbey
Outcome results
None listed