Prazosin for Alcohol Use Disorder With Withdrawal Symptoms

NCT04793685 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2000029805R01AA029113-01
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

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 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.

Conditions

Alcohol Withdrawal

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Percent Any Drinking Days

  after full dose in weeks 3-12 of treatment period

• Average Drinks per Drinking Day

  after full dose in weeks 3-12 treatment period

Other Outcomes (1)

• Percent of Subjects with no Heavy Drinking Days

  weeks 3- 12

Study Arms (2)

Active Drug

EXPERIMENTAL

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; Behavioral: 12-Step Facilitation with Relapse Prevention and Contingency Management

Placebo Drug

PLACEBO COMPARATOR

Placebo for 12 weeks.

Behavioral: 12-Step Facilitation with Relapse Prevention and Contingency Management

Interventions

Prazosin DRUG

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.

Also known as: Minipress

Active Drug

12-Step Facilitation with Relapse Prevention and Contingency Management BEHAVIORAL

12-Step Facilitation and relapse prevention weekly support and Contingency Management for each weekly appointment to support treatment attendance for all subjects.

Active Drug; Placebo Drug

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Yale University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (2)

The Yale Stress Center: Yale University

New Haven, Connecticut, 06519, United States

RECRUITING

The Yale Stress Center: Yale University

New Haven, Connecticut, 06519, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 33207935 BACKGROUND

MeSH Terms

Interventions

Prazosin; Secondary Prevention

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Public Health Practice; Public Health; Environment and Public Health

Study Officials

• David Fiellin, MD

  Yale University

  STUDY DIRECTOR

• Gretchen Hermes, MD

  Yale University

  STUDY DIRECTOR

Central Study Contacts

RAJITA SINHA, PhD

CONTACT

12038592840; rajita.sinha@yale.edu

Rachel Hart, MA

CONTACT

203-641-4922; rachel.hart@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients randomized to Prazosin 16 mg/day titrated over 2 weeks versus placebo taken for 12 weeks with week 12 taper of study medications.

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 11, 2021
• Study Start: July 1, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR
• 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.
• 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.

Locations

US (2)