Clinical trial NCT01437046: Doxazosin an a1 Antagonist for Alcohol Dependence
Official title: Doxazosin an a1 Antagonist for Alcohol Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcohol Dependence
Anxiety
Keywords: Alcohol drinking
Alcohol craving
Lead sponsor: Brown University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2011-09-20
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: drinking days per week (DDW)
timeFrame: 16 weeks
measure: drinks per week (DPW)
timeFrame: 16 weeks
Secondary outcomes:
measure: alcohol craving
timeFrame: 16 weeks
measure: anxiety
timeFrame: 16 weeks
measure: Adverse Events
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Providence
country: United States
facility: Brown University Center for Alcohol and Addiction Studies
state: Rhode Island
Study officials:
References: