Pregnenolone for the Treatment of Alcohol Use Disorder

This Phase 2 randomized cotrolled trial (RCT) will assess the safety and efficacy of pregnenolone (PREG; 300 mg/day, b.i.d dosing) vs. placebo (PBO) over a 12 week treatment period, and at 1-month post-treatment follow-up in individuals with Alcohol Use Disorder (AUD).

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Pregnenolone

Detailed Description

In this Phase 2 single-site randomized controlled trial (RCT), men and women with Alcohol Use Disorder (AUD) will be enrolled in a 12 week trial with a 1-month follow-up assessment. Participants will be randomly assigned to 300mg pregnenolone (PREG) treatment b.i.d., or Placebo (PBO). All participants will be assessed 2x weekly and also receive behavior counseling to support recovery. The study aims to examine a) the safety and tolerability; b) efficacy on alcohol use outcomes; and c) effects on alcohol craving, anxiety, depression and physical well-being of 300mg PREG vs. PBO in men and women with AUD over the 12-week treatment period and at the 1-month follow up post-treatment period.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rajita Sinha, PHD; Phone Number: 203-737-5805; Email: rajita.sinha@yale.edu
• Study Contact Backup: Name: Verica Milivojevic, PhD; Phone Number: 203-737-1176; Email: verica.milivojevic@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • The Yale Stress Center: Yale University
      • Principal Investigator: Rajita Sinha, PhD
      • Contact: Rachel Hart, MS; Phone Number: 203-737-4791; Email: rachel.hart@yale.edu
      • Contact: Verica Milivojevic, PhD; Phone Number: 12037371176; Email: verica.milivojevic@yale.edu
      • Principal Investigator: Verica Milivojevic, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and females, aged 18-70 years;
• Regular weekly use of alcohol at least 3X weekly or more at treatment entry;
• Must meet current DSM-5 criteria for moderate to severe Alcohol Use Disorders (AUDs) using SCID-I for DSM-5;
• No health conditions that would impact trial participation as verified by screening and physical examination and absence of any of the exclusion criterions outlined below;
• Able to read English and complete study evaluations;
• Able to provide informed written and verbal consent.

Exclusion Criteria:

• Meet current criteria for moderate to severe substance use disorders from use of any other psychoactive substance, excluding nicotine and cannabis use disorder;
• Current use of opioids;
• Regular use of anticonvulsants, sedatives or hypnotics, oral prescription analgesics (other than non-steroidal anti-inflammatory drugs), topiramate, baclofen;
• Regular use of steroidal supplements and steroid medications interacting with study medications based on clinical judgement of study physician (excluding hormonal contraceptives in women);
• Psychotic or otherwise severely psychiatrically disabled (i.e., suicidal, homicidal, current mania);
• Significant underlying medical conditions such as cerebral, renal, thyroid or cardiac pathology which in the opinion of study physician would preclude patient from fully cooperating or be of potential harm during the course of the study, but stable, prescribed anti-hypertensives. cardiovascular and diabetes medications will be allowed after review by study physician;
• Any psychotic disorder or current Axis I psychiatric disorders requiring specific acute attention, including need for psychiatric medications, but stable, prescribed antidepressants and anti-anxiety medication to treat co-occurring psychiatric disorders will be allowed;
• Women who are pregnant, nursing or refuse to use a reliable form of birth control (as assessed by urine pregnancy tests during initial medical evaluation, and assessed every two weeks during the course of the study).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: patients receiving 300mg PREG; Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily.	Drug: Pregnenolone; 300mg
Placebo Comparator: placebo; Patients randomly assigned to receive a placebo daily.	Drug: Placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects with no Heavy Drinking Days	Pregnenolone versus Placebo treated subjects will be compared on any days of heavy drinking which is defined by 5 or more drinks per day in men and 4 or more drinks/day in women. This will be measured by the Percent of Subjects with no Heavy Drinking Days (PSNHDD) over a 12 week period.	12 weeks
Safety of pregnenolone	The Systematic Assessment of Treatment Emergent Events (SAFTEE) Questionnaire will be used to assess adverse events weekly during the trial.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Heavy Drinking Days	Percent of overall days with heavy drinking days (defined by 5 or more drinks per day in men and 4 or more drinks/day in women).	12 weeks
Percent Any Drinking Days	Percent of any drinking days over a 12 week period.	12 weeks
Average Drinks per Day	The average number of drinks consumed per day assessed weekly over the treatment period.	12 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: March 10, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 23, 2023

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Gonadal Steroid Hormones; Gonadal Hormones; Pregnenes; Hydroxycorticosteroids; Adrenal Cortex Hormones; Progesterone Congeners; Pregnenolone
• Other Study ID Numbers: 2000034929; R01AA030923 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes