Pharmacogenetic Trial of Doxazosin for Treatment of Cocaine Abuse

• ClinicalTrials.gov Identifier: NCT01953432
• Recruitment Status: Completed
• First Posted: October 1, 2013
• Results First Posted: February 20, 2020
• Last Update Posted: February 20, 2020
• Sponsor: VA Office of Research and Development
• Collaborator: Baylor College of Medicine
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cocaine Dependence	Drug: Doxazosin; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pharmacogenetic Trial of Noradrenergic Medication for Treatment of Cocaine Abuse
• Actual Study Start Date: April 1, 2014
• Actual Primary Completion Date: September 1, 2017
• Actual Study Completion Date: October 1, 2017

Arms and Interventions

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 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.; Other Name: Cardura (Doxazosin Mesylate)
Placebo Comparator: Placebo; Matched placebo daily dosing.	Drug: Placebo; Matched placebo daily dosing; Other Name: Sugar pills (capsule)

Outcome Measures

Primary Outcome Measures :

1. Percentage of Cocaine-positive Urines [ Time Frame: Up to 12 weeks, or for the duration of the participant's involvement in the study ]
   Over period of 12 weeks with 43 participants total (Doxazosin group = 22; Placebo group = 21), the overall percentage of cocaine positive urines per treatment group

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Texas

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States, 77030

Sponsors and Collaborators

VA Office of Research and Development

Baylor College of Medicine

Investigators

• Principal Investigator: Daryl I Shorter, MD; Michael E. DeBakey VA Medical Center, Houston, TX

  Study Documents (Full-Text)

Documents provided by VA Office of Research and Development:

Study Protocol and Statistical Analysis Plan  [PDF] March 14, 2019

More Information

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01953432
• Other Study ID Numbers: CLIN-014-12F; 1IK2CX000946-01 ( U.S. NIH Grant/Contract )
• First Posted: October 1, 2013
• Results First Posted: February 20, 2020
• Last Update Posted: February 20, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by VA Office of Research and Development:

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

Additional relevant MeSH terms:

Cocaine-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Doxazosin; Antihypertensive Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs