Alcohol Use Disorder (AUD)Phase 2PREG-AUD-RO1NCT07734701
Pregnenolone Treatment for Alcohol Use Disorder and Major Depressive Disorder
A Phase 2 study testing Pregnenolone in people with Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD), run by Sherwood Brown, MD, PhD at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 55 years
- Conditions the study is for
- Alcohol Use Disorder (AUD), Major Depressive Disorder (MDD)
- What is being tested?
- Pregnenolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2026to Mar 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites
UT Southwestern Medical Center
Dallas, Texas, 75390
E. Sherwood Brown, 214-645-6950, SHERWOOD.BROWN@UTSouthwestern.edu
E. Sherwood Brown
University of Texas at Dallas
Richardson, Texas, 75080
Francesca Filbey, 972-883-2313, francesca.filbey@utdallas.edu
Francesca Filbey
About this study
Official title: Targeting Neurosteroid Pathways in Alcohol Use Disorder: Clinical and Neural Impact of Pregnenolone Therapy
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.
Read the 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.
- Being tested
- Pregnenolone, Placebo
- Keywords
- Pregnenolone, Alcohol Use Disorder, Major Depressive Disorder, Neurosteroids, fMRI, Anxiety, Substance Use Disorders
- Medical subject headings
- Alcoholism, Depressive Disorder, Major, Anxiety Disorders, Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregnenoloneDrug
Pregnenolone 500 mg/day administered as 250 mg twice daily for 12 weeks.
PlaceboDrug
Matching placebo capsules administered twice daily for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pregnenolone | Experimental | Participants will receive pregnenolone 500 mg/day administered as 250 mg twice daily for 12 weeks. Receives: Drug: Pregnenolone |
| Placebo | Placebo comparator | Participants will receive matching placebo capsules administered twice daily for 12 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alcohol Consumption
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).
Measured: Baseline to Week 12
Secondary outcomes (4)
Alcohol Craving
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.
Measured: Baseline to Week 12
Depressive Symptom Severity
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.
Measured: Baseline to Week 12
Anxiety Symptom Severity
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.
Measured: Baseline to Week 12
Amygdala-Prefrontal Functional Connectivity
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.
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2026
- Study startOct 2026 (estimated)
- Primary completionMar 2031 (estimated)
- Study completionMar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alcohol Use Disorder (AUD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized in a parallel-group design to receive either pregnenolone 500 mg/day or matching placebo for 12 weeks.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sherwood Brown, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- The University of Texas at Dallas, Duke University, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor-investigator, Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07734701
- Sponsor's protocol ID
- STU20261165
- Other IDs
- R01AA033156
- Acronym
- PREG-AUD-RO1
- Status last verified
- Aug 2026
- First submitted
- 8 Jul 2026
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Brown ES, Park J, Marx CE, Hynan LS, Gardner C, Davila D, Nakamura A, Sunderajan P, Lo A, Holmes T. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014 Nov;39(12):2867-73. doi: 10.1038/npp.2014.138. Epub 2014 Jun 11.
PubMed 24917198Mason BL, Van Enkevort E, Filbey F, Marx CE, Park J, Nakamura A, Sunderajan P, Brown ES. Neurosteroid Levels in Patients With Bipolar Disorder and a History of Cannabis Use Disorders. J Clin Psychopharmacol. 2017 Dec;37(6):684-688. doi: 10.1097/JCP.0000000000000793.
PubMed 29045302
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Neurosteroid Pathways in Alcohol Use Disorder: Clinical and Neural Impact of Pregnenolone Therapy
- ClinicalTrials.gov ID
- NCT07734701
- Acronym / sponsor ID
- PREG-AUD-RO1 / STU20261165
- Keywords
- Pregnenolone, Alcohol Use Disorder, Major Depressive Disorder, Neurosteroids, fMRI, Anxiety, Substance Use Disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Sherwood Brown, MD, PhDUniversity, hospital or other
- Collaborators
- The University of Texas at Dallas, Duke University, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- Oct 2026 (estimated)
- Primary completion
- Mar 2031 (estimated)
- Study completion
- Mar 2031 (estimated)
- First posted
- 29 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomized in a parallel-group design to receive either pregnenolone 500 mg/day or matching placebo for 12 weeks.
| Arm | Type | Receives |
|---|---|---|
| Pregnenolone | Experimental | Drug: PregnenoloneParticipants will receive pregnenolone 500 mg/day administered as 250 mg twice daily for 12 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive matching placebo capsules administered twice daily for 12 weeks. |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PregnenolonePregnenolone 500 mg/day administered as 250 mg twice daily for 12 weeks. | Drug | Pregnenolone |
| PlaceboMatching placebo capsules administered twice daily for 12 weeks. | Drug | Placebo |
Primary outcome
Alcohol Consumption
Time frame: 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).
4 secondary outcomes
Alcohol Craving
Time frame: Baseline to Week 12
Depressive Symptom Severity
Time frame: Baseline to Week 12
Anxiety Symptom Severity
Time frame: Baseline to Week 12
Amygdala-Prefrontal Functional Connectivity
Time frame: Baseline and Week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Background: PubMed 24917198Brown ES, Park J, Marx CE, Hynan LS, Gardner C, Davila D, Nakamura A, Sunderajan P, Lo A, Holmes T. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014 Nov;39(12):2867-73. doi: 10.1038/npp.2014.138. Epub 2014 Jun 11.
- Background: PubMed 29045302Mason BL, Van Enkevort E, Filbey F, Marx CE, Park J, Nakamura A, Sunderajan P, Brown ES. Neurosteroid Levels in Patients With Bipolar Disorder and a History of Cannabis Use Disorders. J Clin Psychopharmacol. 2017 Dec;37(6):684-688. doi: 10.1097/JCP.0000000000000793.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pregnenolone in people with Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD), run by Sherwood Brown, MD, PhD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact E. Sherwood Brown (214-645-6950, SHERWOOD.BROWN@UTSouthwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alcohol Consumption (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07734701, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.