Pharmacogenetics of Doxazosin for Cocaine Dependence

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Baylor College of Medicine
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Thomas R. Kosten, MD, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01145183
First received: June 15, 2010
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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.


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: Diagnostic
Official Title: H-26605: Pharmacogenetics of Doxazosin for Cocaine Dependence

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • The urine drug screen results and self reports of cocaine and other drug use and cravings [ Time Frame: through out study ] [ Designated as safety issue: No ]
    The urine toxicology tests and scales to report drug use will be performed through out study.


Secondary Outcome Measures:
  • Adverse events reports [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
    Doxazosin will be well tolerated without significant side effects as we increased to our target dose of 8 mg Doxazosin daily


Estimated Enrollment: 100
Study Start Date: March 2010
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (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 6mg-8mg daily dosing until week 13. The subjects will undergo the discontinuation from the study medication during weeks 14 -17.
Other Name: Cardura (Doxazosin Mesylate)
Placebo Comparator: Placebo
Matched placebo daily dosing.
Drug: Placebo
Matched placebo daily dosing
Other Name: sugarpills ( Capsules)

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 17-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 4 week washout period(weeks 14-17). 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 2mg/week induction rate for 3 weeks, according to their randomized assignments, and are maintained on these agents through week 13. At the end of the study (weeks 14-17), participants will undergo discontinuation from active/placebo medication over a 4-week period. Subjects who wish to be transferred to an appropriate treatment program or treatment-research program will be helped with referral during the 4 week period (weeks 14-17).

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 including Viagra, except thiazides, 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: NCT01145183

Contacts
Contact: Coreen Domingo, DrPH 713-791-1414 ext 5054 CDomingo@bcm.edu
Contact: Jose Perez, BA 713-794-7497 japerez@bcm.edu

Locations
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Coreen B Domingo, DPH    713-791-1414 ext 5054    cdomingo@bcm.edu   
Contact: Jose Perez, BA    713-794-7497    Japerez@bcm.edu   
Sub-Investigator: Coreen B Domingo, DPH         
Principal Investigator: Thomas R Kosten, MD         
Sub-Investigator: Daryl Shorter, MD         
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Thomas R. Kosten, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Thomas R. Kosten, MD, Waggoner Chair and Professor of Psychiatry, Neuroscience, Pharmacology, Immunology and Pathology, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01145183     History of Changes
Other Study ID Numbers: P50DA18197-05, P50DA018197-05, P50DA018197, DPMC
Study First Received: June 15, 2010
Last Updated: July 17, 2014
Health Authority: United States: Federal Government

Keywords provided by Baylor College of Medicine:
Cocaine Dependence
Substance Related Disorders
genotype

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

ClinicalTrials.gov processed this record on October 23, 2014