Doxazosin an a1 Antagonist for Alcohol Dependence

August 14, 2025 updated by: Carolina L Haass-Koffler, Brown University
Norepinephrine system represents an important treatment target for alcohol dependence (AD) and the α1 -blocker prazosin may reduce alcohol drinking in rodents and alcoholic patients. The α1 -blocker doxazosin demonstrates a more favorable pharmacokinetic profile than prazosin, but has never been studied for AD. A double-blind placebo-controlled randomized clinical trial was designed in AD individuals seeking outpatient treatment. Doxazosin or matched placebo was titrated to 16 mg/day (or maximum tolerable dose). Drinks per week (DPW) and heavy drinking days (HDD) per week were the primary outcomes. Family history density of alcoholism (FHDA), severity of AD and gender were a priori moderators.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Pre-clinical and clinical evidence has clearly demonstrated that the noradrenergic (NE) system is involved in the neurobiology of AD, thus representing an interesting new pharmacotherapy target and the theoretical rationale for this proposal. Consistent with the concept that the NE system may represent a new pharmacological target for AD, recent studies have shown that the prototype alpha-1 NE receptor antagonist prazosin reduces alcohol drinking in different animal models. Furthermore, clinical evidence has also confirmed that prazosin appears to be efficacious in reducing alcohol consumption in alcohol-dependent individuals. While prazosin has a significant side effect profile and must be taken three times a day, no other α1-blockers have been investigated in alcohol research. Prazosin is a short-acting α1-blocker approved to treat hypertension (HTN) and benign prostatic hyperplasia (BPH). After the approval of prazosin in the 70's, other selective α1-blockers have been developed to treat HTN and/or BPH. Among them, doxazosin has shown a more manageable and safer profile than prazosin. In fact, doxazosin is a long-acting α1-blocker, thus it is taken only once/day. Doxazosin is also less likely to give hypotensive side-effects. Thus, doxazosin is more commonly used in clinical practice to treat HTN and/or BPH, than short-acting α1-blockers, such as prazosin. Poor adherence to medications and/or side-effects represent important factors limiting the effectiveness of pharmacotherapies for patients with AD. If effective for AD, doxazosin may represent a simple, manageable and safe medication, which might be more easily transferable to clinical practice. However, doxazosin has never been tested in AD. This project is a 10-week, double-blind, placebo-controlled, between-subject randomized clinical trial with doxazosin (16mg once/day) in alcohol dependent (AD) individuals. This study attempts to address whether doxazosin is an effective and safe pharmacotherapy for AD.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
41

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Brown University Center for Alcohol and Addiction Studies
      • Providence, Rhode Island, United States, 02912
        • Brown University Center for Alcohol and Addiction Studies

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • age ≥18
  • females must be post-menopausal for ≥1 year, surgically sterile, or practicing a birth control before entry and throughout the study; have a negative urine pregnancy test at screening and before randomization
  • good health (confirmed by medical history, physical, ECG, blood/urine labs)
  • DSM-IV diagnosis of AD
  • average of ≥4 drinks/d for women and ≥5 drinks/d for men during 30 days within the 90 days prior to screening
  • desire to reduce or quit drinking.

Exclusion Criteria:

  • females who are of child bearing potential and not practicing effective birth control
  • lifetime DSM-IV diagnosis of schizophrenia, bipolar disorder, or other psychosis
  • recent (past 6 months) DSM-IV diagnosis of any anxiety disorder or major depression
  • in the investigators' opinion, risk of suicide (e.g. active plan, or recent attempt in last year)
  • DSM-IV diagnosis of dependence on any psychoactive substance other than alcohol and nicotine
  • positive urine screen for any illegal substance other than marijuana
  • history of hospitalization for alcohol intoxication delirium, seizure or alcohol withdrawal delirium
  • Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) score ≥10, at any assessment
  • treatment with naltrexone, acamprosate, topiramate, disulfiram within 1 month prior to Wk 00
  • current use of psychotropic medications or drugs that interfere with doxazosin's metabolism
  • use of PDE5 inhibitor erectile dysfunction drugs (e.g. sildenafil)
  • treatment with any antihypertensive drug and/or any α-blocker for BPH or sleep problems (e.g. trazodone)
  • baseline hypotension
  • history of allergy to any α-blocker
  • contraindications to take doxazosin (history of fainting and/or syncopal attacks, heart failure, significant liver diseases)
  • serious illnesses, e.g. kidney failure, epilepsy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Doxazosin
Doxazosin Capsule 16mg/day 10 weeks.
Drug: Doxazosin
Doxazosin were prepared as opaque capsules by a compounding pharmacy and inserted into blister packs. Consistent with the recommended titration, doxazosin was titrated up to 16 mg daily (or maximum tolerable dose) during the first 4 weeks. A 1-week downward titration for safety reasons was also planned. Study medication adherence was assessed by self-report and pill count. Additionally, capsules contained 25mg riboflavin as a marker of adherence through urine sample.
Other Names:
  • Cardura
Placebo Comparator: Placebo
Placebo (lactose capsules designed to be the same as experimental drug given the same exact way over 10 weeks.
Drug: Placebo
Matched placebo were prepared as opaque capsules by a compounding pharmacy and inserted into blister packs. Consistent with the recommended titration, doxazosin or matched placebo was titrated up to 16 mg daily (or maximum tolerable dose) during the first 4 weeks. A 1-week downward titration for safety reasons was also planned. Study medication adherence was assessed by self-report and pill count. Additionally, capsules contained 25mg riboflavin as a marker of adherence through urine sample.
Other Names:
  • Lactose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
drinking days per week (DDW)
Time Frame: 16 weeks
whether doxazosin, as compared to placebo, decreases the number of drinking days per week (DDW), as measured by the timeline follow-back (TLFB). A drink is defined as a Standard Drinking Unit (SDU).
16 weeks
drinks per week (DPW)
Time Frame: 16 weeks
whether doxazosin, as compared to placebo, decreases the number of drinks per week (DPW), measured by the TLFB
16 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
alcohol craving
Time Frame: 16 weeks
whether doxazosin, as compared to placebo, results in diminished alcohol craving, as measured by the Obsessive Compulsive Drinking Scale (OCDS)
16 weeks
anxiety
Time Frame: 16 weeks
whether doxazosin, as compared to placebo, results in diminished anxiety scores, measured by the Hamilton Anxiety Scale (HAMA).
16 weeks
Adverse Events
Time Frame: 16 weeks
whether doxazosin, as compared to placebo, increases the frequency and intensity of Adverse Events (AE).
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Brown University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: GEORGE A KENNA, PhD RPh, Brown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 19, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 19, 2011

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 20, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 18, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 14, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1101000328
  • 1R21AA019994-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

email the PI to make arrangements for sharing the available database.

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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