Doxazosin an a1 Antagonist for Alcohol Dependence
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.
|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|
- 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
- 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).
|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)|
|Placebo Comparator: Placebo||Drug: Placebo|
|Contact: Lorenzo Leggio, MD||401-863-6638|
|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|