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

Study Overview
=================
Brief Summary
-----------------
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).

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.

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

Conditions
-----------------
Alcohol Use Disorder

Intervention / Treatment
-----------------
* Drug: Pregnenolone300
* Drug: Pregnenolone500
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 68 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Double-blind, placebo-controlled, parallel design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: patients receiving 300mg PREG<br>Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. | Drug: Pregnenolone300<br>* 300mg<br>|
| Active Comparator: patients receiving 500mg PREG<br>Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. | Drug: Pregnenolone500<br>* 500mg<br>|
| Placebo Comparator: placebo<br>Patients randomly assigned to receive a placebo daily. | Drug: Placebo<br>* placebo<br>|

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 |