Pregnenolone Treatment for Alcohol Use Disorder and Major Depressive Disorder (PREG-AUD-RO1)

Sherwood Brown, MD, PhD

Status and phase: Begins enrollment this month; Phase 2

Conditions: Alcohol Use Disorder (AUD); Major Depressive Disorder (MDD)

Treatments: Drug: Placebo; Drug: Pregnenolone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07734701

STU20261165

R01AA033156 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 21 to 55 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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100 participants in 2 patient groups, including a placebo group

Pregnenolone

Experimental group

Description:

Participants will receive pregnenolone 500 mg/day administered as 250 mg twice daily for 12 weeks.

Treatment:

Drug: Pregnenolone

Placebo

Placebo Comparator group

Description:

Participants will receive matching placebo capsules administered twice daily for 12 weeks.

Treatment:

Drug: Placebo