Pharmacogenetic Trial of Doxazosin for Treatment of Cocaine Abuse
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Pharmacogenetic Trial of Noradrenergic Medication for Treatment of Cocaine Abuse|
- Reduction in cocaine use [ Time Frame: Up to 13 weeks, or for the duration of the participant's involvement in the study ] [ Designated as safety issue: No ]Reduction in cocaine use and abstinence rates as assessed by thrice-weekly urine drug screen and self-report
- Treatment Retention [ Time Frame: Up to 13 weeks, or for the duration of the participant's involvement in the study ] [ Designated as safety issue: No ]Weeks in treatment
- Adverse events [ Time Frame: Up to 13 weeks, or for the duration of the participant's involvement in the study ] [ Designated as safety issue: Yes ]Reported medication side effects (medication tolerability)
- Changes in cocaine craving [ Time Frame: Up to 13 weeks, or for the duration of the participant's involvement in the study ] [ Designated as safety issue: No ]Self-report of level of craving using visual analog scale (VAS)
|Study Start Date:||April 2014|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
Doxazosin is a long-acting and selective alpha 1-NE blocker, which inhibits the binding of norepinephrine to alpha receptors in the autonomic nervous system.
Doxazosin is initiated at 2 mg/wk, and titrated up to a maximum of 8 mg/day over approximately 4 weeks. Participants will be maintained on 8mg daily dosing until week 13. The subjects will undergo the discontinuation from the study medication during weeks 14 -15.
Other Name: Cardura (Doxazosin Mesylate)
Placebo Comparator: Placebo
Matched placebo daily dosing.
Matched placebo daily dosing
Other Name: Sugar pills (capsule)
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01953432
|Contact: Daryl I Shorter, MD||(713) 791-1414 ext 3645||Daryl.Shorter@va.gov|
|Contact: Thomas Kosten, MD||(713) firstname.lastname@example.org|
|United States, Texas|
|Michael E. DeBakey VA Medical Center, Houston, TX||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Daryl I Shorter, MD 713-791-1414 ext 3645 Daryl.Shorter@va.gov|
|Contact: Timothy R Shutter, MA (713) 791-1414 ext 4513 email@example.com|
|Principal Investigator: Daryl I Shorter, MD|
|Principal Investigator:||Daryl I Shorter, MD||Michael E. DeBakey VA Medical Center, Houston, TX|