Prazosin for Alcohol Use Disorder With Withdrawal Symptoms

Study Overview
=================
Brief Summary
-----------------
This is a Phase 2 single site randomized clinical trial (RCT) to be supported by a new NIH-NIAAA grant, R01-AA029113-01, to assess the efficacy of Prazosin (16mg/day) versus Placebo over a 12 week treatment period, followed by a 1- and 3- month assessments post-treatment for individuals with Alcohol Use Disorder (AUD) and history of past or current evidence of alcohol withdrawal symptoms. If medical detoxification is required for any patient, patients would be enrolled after medical detoxification. for those not requiring detoxification, they will be enrolled directly without any requirement of alcohol abstinence. All patients will be provided behavioral counseling weekly with a trained counselor to support recovery during the trial. Primary outcomes will be percent of subjects no heavy drinking days (PSNHDD) and %of any drinking and heavy drinking days as well as secondary outcomes of craving, mood, anxiety and sleep problems.

Detailed Description
-----------------
In this Phase 2 single site RCT, individuals with moderate to severe alcohol use disorder (AUD) and presenc eof alcohol withdrawal symptoms (greater than 3 symptoms or more) will be enrolled in a 12 week trial with a 1- and 3- month follow up assessment. Subjects will be randomized to 16 mh /day Prazosin (PR) or Placebo (PBO) with a 2 week titration period and week 12 taper. All subjects will be assessed 2X weekly and also provided weekly behavioral counseling to support recovery.

Official Title
-----------------
Prazosin Treatment for Alcohol Use Disorder With Alcohol Withdrawal Symptoms

Conditions
-----------------
Alcohol Withdrawal

Intervention / Treatment
-----------------
* Drug: Prazosin
* Behavioral: 12-Step Facilitation with Relapse Prevention and Contingency Management


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Alcohol Withdrawal (AW) scores of 3 or more on the CIWA-Ar at treatment entry and 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 Disorder (AUD) using SCID-I for DSM-5; No health conditions that would impact trial participation as verified by screening and physical examination; 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 another psychoactive substance, excluding nicotine; Current use of opioids or past history of opioid use disorder; Regular use of anticonvulsants, sedatives/hypnotics, oral prescription analgesics (other than noon-steroidal antiinflammatory drugs), other antihypertensives, anti-arrythmics, antiretroviral medications, tricyclic antidepressants, acamprosate, naltrexone, antabuse, topiramate, gabapentin, baclofen, varenicline; 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; Any psychotic disorder or current Axis I psychiatric disorders requiring specific attention, including need for psychiatric medications; Hypotensive individuals with sitting blood pressure below 100/50 mmHG; Women who are pregnant, nursing or refuse to use a reliable form of birth control (as assessed by pregnancy tests during initial medical evaluation, and assessed every two weeks during the course of the study).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Drug<br>Prazosin (16mg/day) versus Placebo comparator, administered in t.i.d schedule, in capsules, over a 12 week period, with 2 weeks titration in weeks 1-2 and a 5-day taper in week 12. | Drug: Prazosin<br>* Prazosin (16mg/day) versus Placebo comparator, with a 2 week titration period, 9 weeks at full dose and a 5-day taper in week 12.<br>* Other names: Minipress;Behavioral: 12-Step Facilitation with Relapse Prevention and Contingency Management<br>* 12-Step Facilitation and relapse prevention weekly support and Contingency Management with vouchers for each weekly appointment to support treatment attendance for all subjects.<br>|
| Placebo Comparator: Placebo Drug<br>Placebo for 12 weeks. | Behavioral: 12-Step Facilitation with Relapse Prevention and Contingency Management<br>* 12-Step Facilitation and relapse prevention weekly support and Contingency Management with vouchers for each weekly appointment to support treatment attendance for all subjects.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects with no Heavy Drinking Days | Prazosin 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. | up to 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). | up to 12 weeks | 
| Percent Any Drinking Days | Percent of any drinking days over a 12 week period. | up to 12 weeks | 
| Average Drinks per Day | The average number of drinks consumed per day assessed weekly over the treatment period. | up to 12 weeks |