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Doxazosin an a1 Antagonist for Alcohol Dependence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01437046
Recruitment Status : Completed
First Posted : September 20, 2011
Last Update Posted : July 22, 2015
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
George Kenna, Brown University

Brief Summary:
Only three medications are approved by the Food and Drug Administration (FDA) for the treatment of alcohol dependence (AD), namely disulfiram, naltrexone tablets and injection, and acamprosate, however treatment success has been inconsistent. Thus, there exists a substantial need for discovering ways to provide more effective treatments. 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.

Condition or disease Intervention/treatment Phase
Alcohol Dependence Anxiety Drug: Doxazosin Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Doxazosin an a1 Antagonist for Alcohol Dependence
Study Start Date : November 2011
Actual Primary Completion Date : August 2013
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Doxazosin
Doxazosin 16mg/day
Drug: Doxazosin
Doxazosin 16mg/day

Placebo Comparator: Placebo
Drug: Placebo

Primary Outcome Measures :
  1. 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).

  2. 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

Secondary Outcome Measures :
  1. 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)

  2. anxiety [ Time Frame: 16 weeks ]
    whether doxazosin, as compared to placebo, results in diminished anxiety scores, measured by the Hamilton Anxiety Scale (HAMA).

  3. Adverse Events [ Time Frame: 16 weeks ]
    whether doxazosin, as compared to placebo, increases the frequency and intensity of Adverse Events (AE).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01437046

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United States, Rhode Island
Brown University Center for Alcohol and Addiction Studies
Providence, Rhode Island, United States, 02903
Sponsors and Collaborators
Brown University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

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Responsible Party: George Kenna, PI, Brown University Identifier: NCT01437046    
Other Study ID Numbers: 1101000328
1R21AA019994-01A1 ( U.S. NIH Grant/Contract )
First Posted: September 20, 2011    Key Record Dates
Last Update Posted: July 22, 2015
Last Verified: July 2015
Keywords provided by George Kenna, Brown University:
Alcohol drinking
Alcohol craving
Additional relevant MeSH terms:
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Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Antihypertensive Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action