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Pharmacogenetic Trial of Doxazosin for Treatment of Cocaine Abuse

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01953432
Recruitment Status : Completed
First Posted : October 1, 2013
Last Update Posted : November 30, 2017
Baylor College of Medicine
Information provided by (Responsible Party):
VA Office of Research and Development

Brief 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. The investigators will study the effect of doxazosin, an alpha-1 adrenergic antagonist, in reducing cocaine use and anxiety symptoms among cocaine-dependent individuals. In addition, the investigators will identify genetic subpopulations of participants who preferentially respond to the medication.

Condition or disease Intervention/treatment Phase
Cocaine Dependence Drug: Doxazosin Drug: Placebo Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacogenetic Trial of Noradrenergic Medication for Treatment of Cocaine Abuse
Actual Study Start Date : April 1, 2014
Actual Primary Completion Date : September 1, 2017
Actual Study Completion Date : October 1, 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Doxazosin
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.
Drug: Doxazosin
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.
Drug: Placebo
Matched placebo daily dosing
Other Name: Sugar pills (capsule)

Primary Outcome Measures :
  1. Reduction in cocaine use [ Time Frame: Up to 13 weeks, or for the duration of the participant's involvement in the study ]
    Reduction in cocaine use and abstinence rates as assessed by thrice-weekly urine drug screen and self-report

Secondary Outcome Measures :
  1. Treatment Retention [ Time Frame: Up to 13 weeks, or for the duration of the participant's involvement in the study ]
    Weeks in treatment

  2. Adverse events [ Time Frame: Up to 13 weeks, or for the duration of the participant's involvement in the study ]
    Reported medication side effects (medication tolerability)

  3. Changes in cocaine craving [ Time Frame: Up to 13 weeks, or for the duration of the participant's involvement in the study ]
    Self-report of level of craving using visual analog scale (VAS)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Signed informed consent form and HIPAA authorization form
  2. Subject is cooperative, understands the risks and benefits, and is willing and able to adhere to study requirements
  3. Any race or ethnic origin
  4. Diagnosis of cocaine-dependence according to DSM-IV criteria
  5. Between the ages of 18 and 64
  6. Must be current users of cocaine with self-reported use of cocaine within the last 90 days, or at least one cocaine-positive urine during screening.
  7. 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.
  8. 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.
  9. 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:

  1. Current diagnosis of other drug dependence, especially alcohol or benzodiazepine dependence, or abuse (other than cocaine, tobacco, or cannabis)
  2. 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, a current cardiac condition that in the opinion of the investigator would contraindicate Doxasozin treatment, and those having a high risk of cardiovascular disease, seizure disorders, or another significant underlying medical condition which would contraindicate Doxazosin treatment
  3. Lifetime schizophrenia, bipolar disorder, or other psychotic disorders (excluding substance-induced psychotic disorders)
  4. Actively considering plans of suicidality or homicidality
  5. 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
  6. Subjects who are prescribed certain anti-hypertension drugs (i.e. doxasozin) will be excluded because these medications may interact with Doxazosin's brain effects in reducing cocaine abuse
  7. Subject has participated in another clinical trial or received any other investigational compound within 7 days prior to being randomized into this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01953432

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United States, Texas
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, United States, 77030
Sponsors and Collaborators
VA Office of Research and Development
Baylor College of Medicine
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Principal Investigator: Daryl I Shorter, MD Michael E. DeBakey VA Medical Center, Houston, TX

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Responsible Party: VA Office of Research and Development Identifier: NCT01953432     History of Changes
Other Study ID Numbers: CLIN-014-12F
1IK2CX000946-01 ( U.S. NIH Grant/Contract )
First Posted: October 1, 2013    Key Record Dates
Last Update Posted: November 30, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by VA Office of Research and Development:
Cocaine-Related Disorders
Cardiovascular Agents
Antihypertensive Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Therapeutic Uses
Pharmacologic Actions
Substance-Related Disorders

Additional relevant MeSH terms:
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Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Adrenergic alpha-1 Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Anesthetics, Local
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Agents
Neurotransmitter Agents
Antihypertensive Agents
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents