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Alcohol DependenceEarly Phase 1NCT01437046

Doxazosin an a1 Antagonist for Alcohol Dependence

A Early Phase 1 study testing Doxazosin in people with Alcohol Dependence and Anxiety, run by Brown University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Alcohol Dependence, Anxiety
What is being tested?
Doxazosin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
41 participants
Where
2 sitesUnited States
Study dates
1 Nov 2011to 1 Mar 2015
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 16Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Brown University Center for Alcohol and Addiction Studies

    Providence, Rhode Island, 02903

  • Brown University Center for Alcohol and Addiction Studies

    Providence, Rhode Island, 02912

Other trials in United States

About this study

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.

Read the 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.

Being tested
Doxazosin, Placebo
Keywords
Alcohol drinking, Alcohol craving
Medical subject headings
Alcoholism, Anxiety Disorders, Alcohol Drinking

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DoxazosinDrug

    Also called Cardura

    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.

  • PlaceboDrug

    Also called Lactose

    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.

Study groups in NCT01437046
Study groupRoleWhat they receive
DoxazosinExperimentalDoxazosin Capsule 16mg/day 10 weeks.
Receives: Drug: Doxazosin
PlaceboPlacebo comparatorPlacebo (lactose capsules designed to be the same as experimental drug given the same exact way over 10 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 16 weeks

  2. drinks per week (DPW)

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

    Measured: 16 weeks

Secondary outcomes (3)

  1. alcohol craving

    whether doxazosin, as compared to placebo, results in diminished alcohol craving, as measured by the Obsessive Compulsive Drinking Scale (OCDS)

    Measured: 16 weeks

  2. anxiety

    whether doxazosin, as compared to placebo, results in diminished anxiety scores, measured by the Hamilton Anxiety Scale (HAMA).

    Measured: 16 weeks

  3. Adverse Events

    whether doxazosin, as compared to placebo, increases the frequency and intensity of Adverse Events (AE).

    Measured: 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2011 (estimated)
  2. Study start1 Nov 2011
  3. Primary completion1 Aug 2013
  4. Study completion1 Mar 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01437046
Sponsor's protocol ID
1101000328
Other IDs
1R21AA019994-01A1
Status last verified
Feb 2016
First submitted
19 Sep 2011
Last updated
18 Aug 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: email the PI to make arrangements for sharing the available database.

Publications

  • 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.

    PubMed 26037245

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Doxazosin in people with Alcohol Dependence and Anxiety, run by Brown University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

drinking days per week (DDW) (time frame: 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01437046, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2025.

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