Effectiveness of Memantine in Treating Cocaine-Dependent Individuals - 2

A Double-Blind, Placebo-Controlled Trial of the Effectiveness of Memantine in Treating Cocaine Dependence

Cocaine is one of the most widely abused drugs in the United States. Memantine is a type of drug called an NMDA receptor antagonist. It works by decreasing normal excitement in the brain. NMDA receptor antagonists have shown to reduce cocaine-induced dopamine release in animal models, as well as lessen conditioned cocaine cues. The purpose of this study is to determine the effectiveness of memantine in preventing relapse to cocaine use in cocaine dependent individuals. In addition, this study will determine whether memantine produces better results than a placebo in decreasing cocaine craving, psychological symptoms, functional impairment, and discontinuation of treatment in cocaine dependent individuals.

Study Overview

• Status: Completed
• Conditions: Cocaine-Related Disorders
• Intervention / Treatment: Drug: placebo; Drug: Memantine

Detailed Description

Memantine is a non-competitive NMDA receptor antagonist that works by decreasing normal excitement in the brain. Dopamine plays a role in the rewarding and addictive properties of cocaine, however, past clinical studies have not been successful in using dopamine agonists in treating cocaine dependent individuals. Non-competitive NMDA receptor antagonists have shown to reduce cocaine-induced dopamine release in animal models and lessen conditioned cocaine cues. This study will evaluate memantine in treating cocaine dependent individuals and its ability to prevent relapse to cocaine use. Specifically, the aim of this study is to determine if memantine is superior to placebo in decreasing cocaine craving, psychological symptoms, functional impairment, and discontinuation of treatment for cocaine abuse.

Participants will enter a 2-week, single-blind, placebo lead-in phase, during which they will visit the clinic three times each week. At each study visit, urine samples and other rating assessments will be collected. In addition, participants will attend weekly therapy sessions. In order to continue in the trial, participants are required to attend at least four out of the first six study visits and both therapy sessions. Eligible participants will then be randomly assigned to receive either memantine or placebo for the duration of the 12-week, double-blind phase of the trial. Study visits will continue to occur three times each week; participants will also receive weekly therapy. Memantine will be taken twice each day. Participants who complete the 12-week trial will enter a 2-week lead-out phase, during which they will be tapered back to a placebo in a single-blind manner. Weekly psychotherapy sessions will continue until the end of Week 14.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Research Foundation for Mental Hygiene, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meets DSM-IV criteria for current cocaine dependence
• Use of cocaine at least four days in the month prior to enrollment or episodic cocaine binges of at least $200 worth at least twice each month (confirmed by urine toxicology test)

Exclusion Criteria:

• Meets DSM-IV criteria for major depression, bipolar disorder, schizophrenia, or any psychotic disorder other than transient psychosis due to drug abuse
• History of seizures in the two years prior to enrollment
• History of seizures related to current substance abuse (including cocaine, alcohol, or benzodiazepine)
• History of an allergic reaction to memantine
• Chronic organic mental disorder
• Current significant suicidal risk, history of significant suicidal behavior, or any suicide attempt within the year prior to enrollment
• Pregnant or breastfeeding
• Failure to use adequate contraception
• Unstable physical disorders that might make participation hazardous, such as hypertension, acute hepatitis (individuals with chronic mildly elevated transaminase levels at 2 to 3 times the upper normal limit are not excluded if their PT/PTT is normal), renal impairment, or diabetes
• Current coronary vascular disease, or suspected by an abnormal ECG or history of cardiac symptoms
• Cardiac conduction system disease, as indicated by QRS duration greater than 0.11
• History of failure to respond to a previous trial with memantine
• Currently meets DSM-IV criteria for substance dependence or abuse disorder other than nicotine or marijuana
• Currently taking psychotropic medications, excluding zolpidem or trazodone for insomnia

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
Placebo Comparator: Placebo	Drug: placebo; placebo
Experimental: Memantine	Drug: Memantine; Memantine; Other Names: Memantine 40mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly Cocaine Use	Mean number of cocaine using days per week based on self reported use verified by cocaine toxicology results.	weekly use during length of study participation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cocaine Abstinence Based on Daily Self Reported Cocaine Use	A binary indicator of sustained abstinence, defined as three consecutive weeks of no cocaine use, obtained by self-report and verified using negative urine toxicology results, at any point of the trial;	reported weekly cocaine use for 12 weeks/ or study participation

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Drug Abuse (NIDA); Research Foundation for Mental Hygiene, Inc.

Publications and helpful links

Helpful Links

• Substance Treatment and Abuse Research Service (STARS)

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: August 23, 2005
• First Submitted That Met QC Criteria: August 23, 2005
• First Posted (Estimate): August 25, 2005

Study Record Updates

• Last Update Posted (Actual): April 24, 2019
• Last Update Submitted That Met QC Criteria: April 22, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: treatment; memantine; Cocaine dependence
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: #4496-NIDA-12761-2; P50DA012761 (U.S. NIH Grant/Contract)