Pharmacogenetic Trial of Doxazosin for Treatment of Cocaine Abuse

NCT ID: NCT01953432

Last Updated: 2020-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-01
• Study Completion Date: 2017-10-01

Brief 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.

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.

This 12-week double-blind, placebo controlled clinical trial will provide treatment for cocaine-dependent patients and includes a 8-week maintenance medication trial (weeks 3-10). At the end of this period, subjects will have a 2-week study medication taper (weeks 11-12). Qualifying subjects will be randomized to receive Doxazosin up to 8 mg/day or placebo.

At the beginning of week 1, participants will receive Doxazosin, or placebo according to their randomized assignments, and are maintained on these agents through week 12. At the end of the study (weeks 11-12), participants will undergo discontinuation from active/inactive medication over a 2-week period. Subjects who wish to be transferred to an appropriate treatment program or research program will be referred to upon request, during the study weeks 11-12.

Conditions

Cocaine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Doxazosin

Intervention Type: DRUG

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.

Placebo

Matched placebo daily dosing.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matched placebo daily dosing

Interventions

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.

Intervention Type: DRUG

Placebo

Matched placebo daily dosing

Intervention Type: DRUG

Other Intervention Names

Cardura (Doxazosin Mesylate); Sugar pills (capsule)

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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daryl I Shorter, MD

Role: PRINCIPAL_INVESTIGATOR

Michael E. DeBakey VA Medical Center, Houston, TX

Locations

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1IK2CX000946-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CLIN-014-12F

Identifier Type: -

Identifier Source: org_study_id