Doxazosin an a1 Antagonist for Alcohol Dependence

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by Brown University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
Brown University
ClinicalTrials.gov Identifier:
NCT01437046
First received: September 19, 2011
Last updated: February 2, 2012
Last verified: September 2011
  Purpose

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 Intervention Phase
Alcohol Dependence
Anxiety
Drug: Doxazosin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Doxazosin an a1 Antagonist for Alcohol Dependence

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • drinking days per week (DDW) [ Designated as safety issue: No ]
    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).

  • drinks per week (DPW) [ Designated as safety issue: No ]
    whether doxazosin, as compared to placebo, decreases the number of drinks per week (DPW), measured by the TLFB


Secondary Outcome Measures:
  • alcohol craving [ Designated as safety issue: No ]
    whether doxazosin, as compared to placebo, results in diminished alcohol craving, as measured by the Obsessive Compulsive Drinking Scale (OCDS)

  • anxiety [ Designated as safety issue: No ]
    whether doxazosin, as compared to placebo, results in diminished anxiety scores, measured by the Hamilton Anxiety Scale (HAMA).

  • Adverse Events [ Designated as safety issue: Yes ]
    whether doxazosin, as compared to placebo, increases the frequency and intensity of Adverse Events (AE).


Estimated Enrollment: 60
Study Start Date: November 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxazosin
Doxazosin 16mg/day
Drug: Doxazosin
Doxazosin 16mg/day
Placebo Comparator: Placebo Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01437046

Contacts
Contact: Lorenzo Leggio, MD 401-863-6638

Locations
United States, Rhode Island
Brown University Center for Alcohol and Addiction Studies Recruiting
Providence, Rhode Island, United States, 02903
Contact: Lorenzo Leggio, MD    401-863-6638      
Principal Investigator: Lorenzo Leggio, MD         
Sub-Investigator: George A. Kenna, PhD, RPh         
Sub-Investigator: Robert M Swift, MD, PhD         
Sub-Investigator: William Zywiak, PhD         
Sponsors and Collaborators
Brown University
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT01437046     History of Changes
Other Study ID Numbers: 1101000328, 1R21AA019994-01A1
Study First Received: September 19, 2011
Last Updated: February 2, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Brown University:
Alcohol drinking
Alcohol craving

Additional relevant MeSH terms:
Alcoholism
Anxiety Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Doxazosin
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014