Pharmacogenetic Trial of Doxazosin for Treatment of Cocaine Abuse
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Intervention: Doxazosin; Placebo
Intervention description: 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.; Matched placebo daily dosing
Intervention MeSH terms: Doxazosin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: 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

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.
    

Eligibility criteria:

        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