Pharmacogenetic Trial of Doxazosin for Treatment of Cocaine Abuse

NCT01953432 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLIN-014-12F1IK2CX000946-01
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Cocaine Dependence

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Cocaine-positive Urines

  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

  Up to 12 weeks, or for the duration of the participant's involvement in the study

Study Arms (2)

Doxazosin

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Matched placebo daily dosing.

Drug: Placebo

Interventions

Doxazosin 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.

Also known as: Cardura (Doxazosin Mesylate)

Doxazosin

Placebo DRUG

Matched placebo daily dosing

Also known as: Sugar pills (capsule)

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent form and HIPAA authorization form
• Subject is cooperative, understands the risks and benefits, and is willing and able to adhere to study requirements
• Any race or ethnic origin
• Diagnosis of cocaine-dependence according to DSM-IV criteria
• Between the ages of 18 and 64
• 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.
• 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.
• 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.

You may not qualify if:

• Current diagnosis of other drug dependence, especially alcohol or benzodiazepine dependence, or abuse (other than cocaine, tobacco, or cannabis)
• 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
• Lifetime schizophrenia, bipolar disorder, or other psychotic disorders (excluding substance-induced psychotic disorders)
• Actively considering plans of suicidality or homicidality
• 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
• 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
• Subject has participated in another clinical trial or received any other investigational compound within 7 days prior to being randomized into this study

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Baylor College of Medicine: collaborator

Study Sites (1)

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders; Substance-Related Disorders

Interventions

Doxazosin; Capsules

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Prazosin; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

There was a protocol amendment and the primary outcome measure was changed. The planned analysis was revised to a Bayesian approach to ensure more robust analysis of data given smaller sample size.

Results Point of Contact

• Title: Daryl Shorter, MD
• Organization: Michael E. DeBakey VA Medical Center

shorter@bcm.edu

713-798-4870

Study Officials

• Daryl I Shorter, MD

  Michael E. DeBakey VA Medical Center, Houston, TX

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2013
• First Posted: October 1, 2013
• Study Start: April 1, 2014
• Primary Completion: September 1, 2017
• Study Completion: October 1, 2017
• Last Updated: February 20, 2020
• Results First Posted: February 20, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)