View Clinical Trial (Medical Research Study)
Doxazosin an a1 Antagonist for Alcohol Dependence
| City: |
|
Providence |
| State: |
|
Rhode Island |
| Zip Code: |
|
02903 |
| Conditions: |
|
Alcohol Dependence - Anxiety |
| 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.
|
| Study Summary: |
|
|
| 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.
|
| NCT ID: |
|
NCT01437046 |
| Primary Contact: |
|
Lorenzo Leggio, MD
Phone: 401-863-6638
|
| Backup Contact: |
|
N/A |
| Location Contact: |
|
Providence, Rhode Island 02903
United States
Lorenzo Leggio, MD
Phone: 401-863-6638
Site Status: Recruiting |
| Data Source: |
|
ClinicalTrials.gov |
| Date Processed: |
|
June 18, 2013 |
| Modifications to this listing: |
|
Only selected fields are shown, please use the link
below to view all information about this clinical trial. |
|
Click to view Full Listing
|