Pharmacogenetics of Doxazosin for Cocaine Dependence

H-26605: Pharmacogenetics of Doxazosin for Cocaine Dependence

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.

Study Overview

• Status: Completed
• Conditions: Cocaine Dependence
• Intervention / Treatment: Drug: Placebo; Drug: Doxazosin

Detailed Description

The NE system, especially the alpha 1-adrenergic receptor, may play an important role in cocaine addiction in humans. The results of this study will provide medical safety data on the duration of the induction schedule that will be optimal for attaining our target dose of 8 mg doxazosin daily and will guide future pharmacotherapy trials using Doxazosin or related alpha 1 receptor antagonists for cocaine addiction.

This 16-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 1 mg study medication/placebo capsules at week 1, with 4mg/week induction rate for weeks, according to their randomized assignments, and are maintained on these agents through week 13. 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).

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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 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.; Other Names: Cardura (Doxazosin Mesylate)
PLACEBO_COMPARATOR: Placebo; Matched placebo daily dosing.	Drug: Placebo; Matched placebo daily dosing; Other Names: sugarpills ( Capsules)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Cocaine Positive Urine Toxicology	Cocaine positive urines	2 weeks blocks throughout study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Adverse effects were closely monitored during each clinic visit throughout this trial. Vital signs including blood pressure (both pre-medication and post-medication) were measured and documented as were concomitant medications.	Pre- and post study medication

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: June 15, 2010
• First Submitted That Met QC Criteria: June 15, 2010
• First Posted (ESTIMATE): June 16, 2010

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2019
• Last Update Submitted That Met QC Criteria: July 18, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: genotype; Cocaine Dependence; Substance Related Disorders
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Doxazosin
• Other Study ID Numbers: P50DA018197-05 (NIH); DPMC (Other Identifier: NIDA); P50DA018197 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO