Doxazosin for Psychostimulant Dependence

Clinical Efficacy of Doxazosin for Psychostimulant Dependence

Psychostimulant dependence is a major public health problem and no medications have been shown to be very effective in treating this disorder. Thus, the investigators wish to study whether a blood pressure drug thought to reduce drug craving through its interaction at particular adrenergic receptors - doxazosin - can dredge cocaine use relative to placebo in psychostimulant dependent participants enrolled in an 8-week, randomized, double blind, placebo-controlled outpatient clinical trial. Our hypothesis is that doxazosin will reduce cocaine use relative to placebo in psychostimulant dependent participants.

Study Overview

• Status: Completed
• Conditions: Methamphetamine or Cocaine Dependence
• Intervention / Treatment: Drug: Doxazosin extended release

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • UAMS Psychiatric Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-55 years old
• Methamphetamine OR cocaine dependence, as assessed by the substance abuse section of the Structured Clinical Interview for DSM-IV.
• At least weekly self-reported methamphetamine OR cocaine use during a preceding three month period
• Urine toxicology screen positive for methamphetamine or methamphetamine metabolite OR cocaine or cocaine metabolite
• Women of childbearing age must have a negative pregnancy test, agree to adequate contraception to prevent pregnancy during the study, agree to monthly pregnancy testing and not be nursing

Exclusion Criteria:

• Suicide attempts within the past 12 months or suicidal ideations or psychotic symptoms in the past 6 months as determined by a study physician.
• Current opioid, alcohol or sedative physical dependence or dependence on both cocaine and methamphetamine
• Major cardiovascular disorder that contraindicates study participation (e.g., history of myocardial infarction, stroke, congestive heart failure, cardiac arrhythmia, significant hypertension [i.e., >170 SBP or >110 DBP] or an unstable medical condition (e.g., untreated bacterial infection) as determined by the study physician.
• Any history or evidence suggestive of seizure disorder or brain injury
• Subjects needing or planning cataract surgery.
• History of schizophrenia, major depression, or bipolar type I disorder
• Organic brain disease or dementia assessed by physician
• Use of medications that would be expected to have major interaction with doxazosin (e.g. atanazavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole or any other potent 3A4 inhibitor.,)
• Any previous medically adverse reaction to methamphetamine or cocaine, including loss of consciousness, chest pain, or epileptic seizure
• Medical contraindication to receiving doxazosin (e.g. liver problems or allergies to other to other quinazolines such as prazosin or terazosin)
• Severe gastrointestinal disorder as determined by physician
• Liver function tests (i.e., liver enzymes) greater than three times normal levels
• Systolic blood pressure > 170 mmHg or < 90 mmHg, diastolic blood pressure > 110 mmHg or < 60 mmHg, or heart rate of > 110 beats/min or < 55 beats/min.
• Supine blood pressure of 100/65 mm Hg or lower, a seated blood pressure of 90/60 mm Hg or lower, or an orthostatic change of >20mm Hg systolic or 10 mm Hg diastolic on standing.
• Have evidence of untreated or unstable medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease
• Have symptomatic HIV or are taking antiretroviral medication
• Have asthma or currently use theophylline or other sympathomimetics
• Participants with estimated glomerular filtration rate < 30 ml/min.
• Pregnant or nursing female

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxazosin; Doxazosin extended release will be administered initially at 4 mg/day. On day 8 the dose is increased to 8 mg/day and the participant is maintained on the study until the end of the trial.	Drug: Doxazosin extended release; initially maintained on doxazosin extended release 4 mg once a day for 7 days, then the dose is increased to 8 mg once per day for the duration of the trial.
Placebo Comparator: Placebo; Participants will be maintained on placebo (cellulose) throughout the trial.	Drug: Doxazosin extended release; initially maintained on doxazosin extended release 4 mg once a day for 7 days, then the dose is increased to 8 mg once per day for the duration of the trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Psychostimulant-positive Urines Over Time	Urine samples positive for methamphetamine or cocaine via twice-weekly urine drug screens. Weekly urine results data were averaged within subjects and the mean proportion across subjects within each group was calculated for graphic representation.	twice-weekly urine samples (8 weeks)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: June 9, 2011
• First Submitted That Met QC Criteria: June 10, 2011
• First Posted (Estimate): June 13, 2011

Study Record Updates

• Last Update Posted (Estimate): July 27, 2015
• Last Update Submitted That Met QC Criteria: July 24, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• 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: 2-P50-DA018197-DoxMeth