Pharmacogenetic Trial of Doxazosin for Treatment of Cocaine Abuse

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by Department of Veterans Affairs
Sponsor:
Collaborator:
Baylor College of Medicine
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01953432
First received: September 10, 2013
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Cocaine Dependence
Drug: Doxazosin
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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)


Estimated Enrollment: 100
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)
Arms Assigned Interventions
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)

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

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01953432

Contacts
Contact: Daryl I Shorter, MD (713) 791-1414 ext 3645 Daryl.Shorter@va.gov
Contact: Thomas Kosten, MD (713) 794-7032 thomas.kosten@va.gov

Locations
United States, Texas
Michael E DeBakey VA Medical Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Daryl I Shorter, MD    713-791-1414 ext 3645    Daryl.Shorter@va.gov   
Contact: Timothy Shutter, MA    (713) 791-1414 ext 4513    shutter@bcm.edu   
Principal Investigator: Daryl I Shorter, MD         
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Daryl I Shorter, MD Michael E. DeBakey VA Medical Center, Houston, TX
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01953432     History of Changes
Other Study ID Numbers: CLIN-014-12F, 1IK2CX000946-01
Study First Received: September 10, 2013
Last Updated: March 28, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Cocaine-Related Disorders
Cocaine
Doxazosin
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:
Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Adrenergic alpha-Antagonists
Doxazosin
Antihypertensive Agents
Cardiovascular Agents
Cocaine
Neurotransmitter Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic Antagonists
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014