Prazosin for Alcohol Use Disorder With Withdrawal Symptoms

Prazosin Treatment for Alcohol Use Disorder With Alcohol Withdrawal Symptoms

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 outcome will be percent of any heavy drinking days and secondary drinking outcomes will be percent of subjects with no heavy drinking days (PSNHDD), avg drinks per drinking day and %of any drinking drinking days as well as additional secondary outcomes of craving, mood and anxiety problems.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Withdrawal
• Intervention / Treatment: Drug: Prazosin; Behavioral: 12-Step Facilitation with Relapse Prevention and Contingency Management

Detailed Description

In this Phase 2 single site RCT, individuals with moderate to severe alcohol use disorder (AUD) and presence of 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 mg /day Prazosin (PR) or Placebo (PBO) with a 2 week titration period and9-week full dose period and week 12 taper. All subjects will be assessed 2X weekly and also provided weekly behavioral counseling to support recovery.

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

Contacts and Locations

• Study Contact: Name: RAJITA SINHA, PhD; Phone Number: 12038592840; Email: rajita.sinha@yale.edu
• Study Contact Backup: Name: Rachel Hart, MA; Phone Number: 203-641-4922; Email: rachel.hart@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: RAJITA SINHA, PHD; Phone Number: 12037375805; Email: rajita.sinha@yale.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Alcohol Withdrawal (AW) scores of 3 or more on the CIWA-Ar at treatment entry OR 2 or more Alcohol Withdrawal Syndrome (AWS) symptoms and regular weekly heavy drinking 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, cocaine and cannabis;
• Current use of illicit /non-prescribed opioids more than 2X/month;
• Regular use of anticonvulsants, sedatives/hypnotics, oral prescription analgesics (other than non-steroidal anti-inflammatory drugs), antiretroviral medications, tricyclic antidepressants, topiramate, baclofen, and regular weekly use of benzodiazepines, as defined by use of three or more times per week;
• Prescribed use of antihypertensive medications that duplicate the mechanism of action at the alpha1 receptor as prazosin or are contraindicated, such as those medications that are also alpha1-adrenergic antagonists (i.e., doxazosin, tamsulosin, terazosin) or are beta-blockers (e.g., propranolol); Potential participants who are prescribed cardiovascular/antihypertensive medications will undergo clinical review by the study PIs and team. Individuals who are prescribed anti-hypertensives that do not duplicate the action of prazosin and are not contraindicated, including ACE inhibitors, angiotensin receptor blockers (ARBs), diuretics, and calcium channel blockers, may be allowed to participate after review from the study physician and principal investigators, with careful monitoring of these individuals' blood pressure at all in-person appointments.
• 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).

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
Experimental: Active Drug; 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; 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.; Other Names: Minipress; Behavioral: 12-Step Facilitation with Relapse Prevention and Contingency Management; 12-Step Facilitation and relapse prevention weekly support and Contingency Management for each weekly appointment to support treatment attendance for all subjects.
Placebo Comparator: Placebo Drug; Placebo for 12 weeks.	Behavioral: 12-Step Facilitation with Relapse Prevention and Contingency Management; 12-Step Facilitation and relapse prevention weekly support and Contingency Management for each weekly appointment to support treatment attendance for all subjects.

What is the study measuring?

Primary 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) after achieving full treatment dose in week 3.	weeks 3 - 12 of full dose treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Any Drinking Days	Percent of any drinking days over a 12 week period.	after full dose in weeks 3-12 of treatment period
Average Drinks per Drinking Day	The average number of drinks consumed per drinking day assessed weekly over the treatment period.	after full dose in weeks 3-12 treatment period

Other 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) after achieving full dose week 3 through 12 time period.	weeks 3- 12

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Study Director: David Fiellin, MD, Yale University; Study Director: Gretchen Hermes, MD, Yale University

Publications and helpful links

General Publications

• Sinha R, Wemm S, Fogelman N, Milivojevic V, Morgan PM, Angarita GA, Hermes G, Fox HC. Moderation of Prazosin's Efficacy by Alcohol Withdrawal Symptoms. Am J Psychiatry. 2021 May 1;178(5):447-458. doi: 10.1176/appi.ajp.2020.20050609. Epub 2020 Nov 19.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 9, 2021
• First Posted (Actual): March 11, 2021

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Substance Withdrawal Syndrome; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Public Health; Environment and Public Health; Health Services; Health Care Facilities Workforce and Services; Preventive Health Services; Quinazolines; Public Health Practice; Prazosin; Secondary Prevention
• Other Study ID Numbers: 2000029805; R01AA029113-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be uploaded to NIAAA data archive (NIAAA-DA housed within the NIMH Data archive (NDa). as per NIH-NIAAA guidelines.
• IPD Sharing Time Frame: Baseline data will be uploaded twice yearly. clinical trial outcome data will be shared after study completion and breaking the blind and completion of final analysis of the main study outcomes.
• IPD Sharing Access Criteria: Access will be provided following the NIH-NIAAA guidelines available at https://grants.nih.gov/grants/guide/notice-files/NOT-AA-19-020.html at the URL below.
• IPD Sharing Supporting Information Type: SAP; CSR

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