Pharmacogenetic Trial of Doxazosin for Treatment of Cocaine Abuse
Information source: Department of Veterans Affairs
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cocaine Dependence
Intervention: Doxazosin (Drug); Placebo (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Department of Veterans Affairs Official(s) and/or principal investigator(s): Daryl I Shorter, MD, Principal Investigator, Affiliation: Michael E. DeBakey VA Medical Center, Houston, TX
Overall contact: Daryl I Shorter, MD, Phone: (713) 791-1414, Ext: 3645, Email: Daryl.Shorter@va.gov
Summary
Cocaine use disorders affect approximately 1. 5 million Americans annually. Currently, there
are no US Food and Drug Administration approved medications for treatment of cocaine
dependence; however, both animal and human studies suggest that medications affecting the
noradrenergic system can reduce cocaine craving and use. We will study the effect of
doxazosin, an alpha-1 adrenergic antagonist, in reducing cocaine use and anxiety symptoms
among cocaine-dependent individuals. In addition, we will identify genetic subpopulations of
participants who preferentially respond to the medication.
Clinical Details
Official title: Pharmacogenetic Trial of Noradrenergic Medication for Treatment of Cocaine Abuse
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Reduction in cocaine use
Secondary outcome: Treatment RetentionAdverse events Changes in cocaine craving
Detailed description:
The noradrenergic system, especially the alpha 1-adrenergic receptor, may play an important
role in cocaine addiction in humans. Doxazosin is a long-acting and selective alpha
1-adrenergic receptor blocker, which inhibits the binding of norepinephrine to alpha
receptors in the autonomic nervous system. This study will evaluate the efficacy of
doxazosin in reducing cocaine-using behavior in treatment seeking cocaine-dependent
individuals, and will guide future pharmacotherapy trials using Doxazosin or related alpha 1
receptor antagonists for treatment of cocaine addiction. Additionally, this study will
identify genetic subpopulations of participants for whom doxazosin is preferentially
effective, specifically examining the R492C functional polymorphism of the ADRA1A gene.
This 15-week double-blind, placebo controlled clinical trial will provide treatment for 100
cocaine-dependent patients and includes a 13 week medication trial (weeks 1-13) and up to 2
week washout period (weeks 14-15). Qualifying subjects will be randomized to receive
Doxazosin 8 mg/day, or placebo during the study participation.
Subjects will be receiving 2 mg study medication/placebo capsules at week 1, with 2mg/week
induction rate for 3 weeks, according to their randomized assignments, and are maintained on
these agents through week 13. During the course of the trial, all participants will receive
manual-guided cognitive behavioral therapy. At the end of the study (weeks 14-15),
participants will undergo discontinuation from active/placebo medication over a 2-week
period. Subjects who wish to be transferred to an appropriate treatment program or
treatment-research program will be helped with referral during the 2 week period (weeks
14-15).
Eligibility
Minimum age: 18 Years.
Maximum age: 64 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Signed informed consent form and HIPAA authorization form
- Subject is cooperative, understands the risks and benefits, and is willing and able
to adhere to study requirements.
- Any race or ethnic origin
- Diagnosis of cocaine-dependence according to DSM-IV criteria
- Between the ages of 18 and 64
- Must be current users of cocaine with self-reported use of cocaine, at least one
cocaine-positive urine during screening, and a score over 3 (which is the cut-off for
diagnosis of cocaine dependence per the DSM IV-R) as assessed with the Severity of
Substance Dependence Scale (Kaye & Darke 2002; Gossop, et al 1995; Gossop, et al.
1997)
- Women of childbearing age are eligible to be included in the study if they have a
negative pregnancy test at screening, agree to adequate contraception to prevent
pregnancy, to have monthly pregnancy tests, and they understand the risk of fetal
toxicity due to medication.
- Must be in good general health as determined by self-report and/or CPRS-based medical
history, general clinical examination conducted by a study physician, and lab tests.
HIV testing will be recommended but is not required for participation in this study.
CPRS medical records will not be accessed until subject signs the ICF.
- Motivated to discontinue or reduce cocaine use during the period of the study, as
evidenced both by the judgment of the Investigator or designee and by the subject's
compliance level with the requirement for attendance at clinic visits, such that
weekly urine sample requirements for inclusion criteria are fully met.
Exclusion Criteria:
- Current diagnosis of other drug dependence, especially alcohol or benzodiazepine
dependence, or abuse (other than cocaine, tobacco, or cannabis).
- Significant medical conditions (e. g., major cardiovascular, renal, endocrine, hepatic
disorders) such as abnormal liver function (with laboratory findings of SGOT or SGPT
greater than three times normal), hypotension or hypertension, a current cardiac
condition, and those having a high risk of cardiovascular disease, seizure disorders,
or another significant underlying medical condition which would contraindicate
Doxazosin treatment.
- Lifetime schizophrenia, bipolar disorder, or other psychotic disorders.
- Actively considering plans of suicidality or homicidality
- Current use of a prescribed psychotropic medication that cannot be discontinued
- Women planning to become pregnant or breastfeed during the study, refusal to use a
reliable form of birth control, or refusal of monthly pregnancy testing
- Subjects who are prescribed certain anti-hypertension drugs including ace inhibitors
and alpha adrenergic blockers will be excluded because these medications may interact
with Doxazosin's brain effects in reducing cocaine abuse.
Locations and Contacts
Daryl I Shorter, MD, Phone: (713) 791-1414, Ext: 3645, Email: Daryl.Shorter@va.gov
Michael E. DeBakey VA Medical Center, Houston, TX, Houston, Texas 77030, United States; Recruiting Daryl I Shorter, MD, Phone: 713-791-1414, Ext: 3645, Email: Daryl.Shorter@va.gov Timothy Shutter, MA, Phone: (713) 791-1414, Ext: 4513, Email: shutter@bcm.edu Daryl I Shorter, MD, Principal Investigator
Additional Information
Starting date: April 2014
Last updated: April 1, 2015
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