Establishing and Eliminating Cue-drug Associations in Human Cocaine Addiction

We will develop a procedure for conditioning cue-cocaine associations in human drug users. Next, we will reactivate that learning and intervene pharmacologically to prevent the reconsolidation of cue-drug memories. We hypothesize that a combined behavioral and pharmacological approach will have significant potential for persistently inhibiting relapse.

Study Overview

• Status: Terminated
• Conditions: Cocaine Dependent Subjects
• Intervention / Treatment: Drug: placebo; Drug: propranolol; Drug: cocaine hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Connecticut Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 - 50 years
2. voluntary, written, informed consent
3. physically healthy by medical history, physical, neurological, ECG, and laboratory examinations
4. DSM-IV criteria for Cocaine Abuse (305.60) or Cocaine Dependence (304.20)
5. recent street cocaine use in excess of that administered in the current study
6. intravenous and/or smoked (crack/freebase) use
7. positive urine toxicology screen for cocaine
8. for females, non-lactating, no longer of child-bearing potential (or agree to practice effective contraception during the study), and a negative serum pregnancy (-HCG) test
9. able to read English and complete study evaluations.

Exclusion Criteria:

1. Other drug dependence (except nicotine)
2. a primary major DSM-IV psychiatric diagnosis (schizophrenia, bipolar disorder, etc.), unrelated to cocaine
3. a history of significant medical (cardiovascular) or neurological illness (e.g., prior myocardial infarction, current active symptoms of cardiovascular disease / angina, evidence of cocaine-related cardiovascular symptoms, prior arrythmias of clinical significance, and/or need for cardiovascular resuscitation, neurovascular events such as transient ischemic attacks, stroke, and/or seizures)
4. current use of psychotropic and/or potentially psychoactive prescription medication
5. seeking treatment for drug abuse/dependence
6. those having contraindications to beta-blocker administration, including diagnoses of asthma, bronchitis, emphysema, or a history of adverse reactions to beta-blockers (including propranolol), as well as those with bradycardia and/or first-degree or greater heart block by ECG

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: propranolol; Drug: cocaine hydrochloride
Experimental: cocaine hydrochloride	Drug: placebo; Drug: propranolol; Drug: cocaine hydrochloride
Experimental: propranolol	Drug: propranolol; Drug: cocaine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of patient controlled analgesic (PCA) pump activations (responses)	Data on cocaine self-administration (total number of responses) will be checked for normality prior to analysis using Kolmogorov-Smirnov statistics and normal probability plots. Data that is not normally distributed will be log transformed. If it remains highly skewed after transformation, it will be analyzed using non-parametric approaches (e.g., a non-parametric, ANOVA-Type Statistic). Normally distributed data will be analyzed employing a mixed model design, 3-way ANOVA with co-factors of placebo vs propranolol (between subjects), non-cocaine predicting cues vs. cocaine predicting cues (within subjects) and non-reactivated cocaine cues vs. reactivated cocaine cues (within subjects).	3 days

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: October 17, 2013
• First Submitted That Met QC Criteria: October 31, 2013
• First Posted (Estimate): November 7, 2013

Study Record Updates

• Last Update Posted (Actual): March 2, 2020
• Last Update Submitted That Met QC Criteria: February 28, 2020
• Last Verified: February 1, 2020

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 beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Anesthetics, Local; Dopamine Uptake Inhibitors; Vasoconstrictor Agents; Propranolol; Cocaine
• Other Study ID Numbers: 1104008404