Pharmacogenetics of Doxazosin for Cocaine Dependence
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Intervention: Doxazosin; Placebo
Intervention description: Doxazosin is initiated at 4 mg/wk, and titrated up to a maximum of 8 mg/day over approximately 2 weeks. Participants will be maintained on 6mg-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: Diagnostic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Cocaine Dependence; Substance Related Disorders; genotype

Summary:

      Doxazosin, an alpha 1-adrenergic receptor antagonist, may play an important role in cocaine
      addiction in humans. This study will evaluate to what extent the prospective screening for
      catecholamine related polymorphisms for alpha 1 NE receptor/transporter, COMT and DBH as main
      targets predict the treatment efficacy of doxazosin for cocaine-using behavior.
    

Eligibility criteria:

        Inclusion Criteria: (1) Signed informed consent form (2) Subject understands the risk and
        benefits and agrees to visit frequency and procedures (3) Male or female (4) Any race or
        ethnic origin (5)Diagnosis of cocaine-dependence according to DSM-IV criteria (6) between
        the ages of 18 and 64 (7)Must be current users of cocaine with self-reported use of cocaine
        at least once weekly for at least one month preceding study entry, cocaine-positive urine
        screen and score over 3 which is the cut-off for diagnosis of cocaine dependence as
        assessed with the Severity of Dependence Scale (Kaye & Darke 2002; Gossop, et al 1995;
        Gossop, et al. 1997) (8)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.

        Exclusion Criteria: (1)Current diagnosis of other drug , especially alcohol or
        benzodiazepine dependence or abuse (other than cocaine or tobacco) (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 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 (3)Lifetime schizophrenia,
        bipolar disorder, or other psychotic disorders (4) Actively considering plans of
        suicidality or homicidality (5) Current use of a prescribed psychotropic medication that
        cannot be discontinued (6) Women planning to become pregnant or breastfeed during the
        study, or refuse to use a reliable form of birth control or refuse monthly pregnancy
        testing (7) Subjects who are prescribed any anti-hypertension drugs, except thiazides, will
        be excluded because these medications may interact with Doxazosin's brain effects in
        reducing cocaine abuse.