NCT01437046

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
41

participants targeted

Target at P50-P75 for early_phase_1

Timeline
Completed

Started Nov 2011

Typical duration for early_phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 19, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 20, 2011

Completed
1 month until next milestone

Study Start

First participant enrolled

November 1, 2011

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2013

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
Last Updated

August 18, 2025

Status Verified

February 1, 2016

Enrollment Period

1.8 years

First QC Date

September 19, 2011

Last Update Submit

August 14, 2025

Conditions

Alcohol DependenceAnxiety

Keywords

Alcohol drinkingAlcohol craving

Outcome Measures

Primary Outcomes (2)

  • drinking days per week (DDW)

    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)

    whether doxazosin, as compared to placebo, decreases the number of drinks per week (DPW), measured by the TLFB

    16 weeks

Secondary Outcomes (3)

  • alcohol craving

    16 weeks

  • anxiety

    16 weeks

  • Adverse Events

    16 weeks

Study Arms (2)

Doxazosin

EXPERIMENTAL

Doxazosin Capsule 16mg/day 10 weeks.

Drug: Doxazosin

Placebo

PLACEBO COMPARATOR

Placebo (lactose capsules designed to be the same as experimental drug given the same exact way over 10 weeks.

Drug: Placebo

Interventions

DoxazosinDRUG

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.

Also known as: Cardura
Doxazosin
PlaceboDRUG

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.

Also known as: Lactose
Placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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)
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Brown University Center for Alcohol and Addiction Studies

Providence, Rhode Island, 02903, United States

Location

Brown University Center for Alcohol and Addiction Studies

Providence, Rhode Island, 02912, United States

Location

Related Publications (1)

  • Kenna GA, Haass-Koffler CL, Zywiak WH, Edwards SM, Brickley MB, Swift RM, Leggio L. Role of the alpha1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial. Addict Biol. 2016 Jul;21(4):904-14. doi: 10.1111/adb.12275. Epub 2015 Jun 2.

    PMID: 26037245BACKGROUND

MeSH Terms

Conditions

AlcoholismAnxiety DisordersAlcohol Drinking

Interventions

DoxazosinLactose

Condition Hierarchy (Ancestors)

Alcohol-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental DisordersDrinking BehaviorBehavior

Intervention Hierarchy (Ancestors)

PrazosinQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDisaccharidesOligosaccharidesPolysaccharidesCarbohydratesSugars

Study Officials

  • GEORGE A KENNA, PhD RPh

    Brown University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
PI

Study Record Dates

First Submitted

September 19, 2011

First Posted

September 20, 2011

Study Start

November 1, 2011

Primary Completion

August 1, 2013

Study Completion

March 1, 2015

Last Updated

August 18, 2025

Record last verified: 2016-02

Data Sharing

IPD Sharing
Will share

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

Locations

US(2)