The Role of Neuroactive Steroids in Stress, Alcohol Craving and Alcohol Use in Alcohol Use Disorders

To use pregnenolone (PREG; 300; 500mg) daily versus placebo (PLA) as a probe to assess the role of neuroactive steroids in individuals with alcohol use disorder (AUD).

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Pregnenolone300; Drug: Pregnenolone500

Detailed Description

The study aims to examine the effects of PREG on a) alcohol craving, mood and neuroendocrine reactivity to brief, guided imagery exposure to stress, drug cues and neutral situations in the laboratory and b) daily alcohol intake, craving, cognition and mood in men and women with AUD; and c) sex differences in all of these outcomes.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • The Yale Stress Center: Yale University
    • New Haven, Connecticut, United States, 06519
      • Yale Stress Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female individuals, ages 18 to 68.
• Subjects must meet current Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-V) criteria for alcohol use disorder; documented positive urine toxicology screen for alcohol at intake or collateral information from family members, significant others, room-mates etc., on recent use.
• Subject has voluntarily given informed consent and signed the informed consent document.
• Able to read English and complete study evaluations.

Exclusion Criteria:

• Women who are pregnant, or nursing or are of childbearing potential and not practicing an effective means of birth control.
• Meet current criteria for use disorder on another psychoactive substance, such as, heroin, amphetamines, hallucinogens/Phencyclidine (PCP), excluding alcohol and nicotine.
• Any current use of opiates or past history of opiate use disorder (assessed via urine toxicology and self report).
• Current use of any psychoactive drugs (urine toxicology), including anxiolytics, naltrexone or antabuse.
• Any psychotic disorder or current Axis I psychiatric symptoms requiring specific attention.
• 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.
• Hypotensive individuals with sitting blood pressure below 90/50 mmHG.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

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: Pregnenolone300; 300mg
Active Comparator: patients receiving 500mg PREG; Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily.	Drug: Pregnenolone500; 500mg
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 Drinking Days	The mean percent drinking days as assessed by self report on daily smartphone monitoring and corroborated by the Substance Use Calendar over the 8 week period.	up to 8 weeks
Percent Heavy Drinking Days	The mean percent heavy drinking days as assessed by self report on daily smartphone monitoring and corroborated by the Substance Use Calendar over the 8 week period.	up to 8 weeks
Number of Drinks Per Drinking Day	Average number of drinks per drinking day as assessed by self report on daily smartphone monitoring and corroborated by the Substance Use Calendar over the 8 week period.	up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Craving	Alcohol craving assessed using the weekly Obsessive Compulsive Drinking Scale (OCDS). This 14-item scale is a quick and reliable self-rating instrument that provides a total and two subscale scores that measure some cognitive aspects of alcohol "craving". Obsessive subscale is the summation of items 1-6 with score range 0-24. Compulsive subscale is the summation of items 7-14 with score range 0-32. Total score range 0-40. Higher scores indicate more obsessions and compulsions with alcohol.	8 week outcome period
Number of Participants With Treatment Emergent Adverse Events	The Systematic Assessment of Treatment Emergent Events (SAFTEE) Questionnaire will be used to assess adverse events weekly during the trial. Data presented here is the number of participants that had any adverse events while on study.	up to 8 weeks
Pregnenolone Levels	Mean of blood levels of study drug assessed at 3 timepoints during the trial up to 8 weeks	up to 8 weeks
Weekly Negative Mood and Anxiety	The Hospital Anxiety and Depression Scale (HADS) will be used; it has 2 subscales (one for depression and one for anxiety) each with 7 items. It is a brief measure of generalized symptoms of anxiety and fear. Respondents indicate how they currently feel and responses are rated on a 4-point Likert scale with total score range from 0 to 21. Total scores are the sum of all items. Total scores are reported. Higher scores indicate higher levels of depression or anxiety.	assessed weekly, score at week 8 reported

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2018
• Primary Completion (Actual): November 1, 2022
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: February 1, 2019
• First Submitted That Met QC Criteria: March 11, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Actual): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism
• Other Study ID Numbers: 1608018179; 1R01AA026514-01A1 (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