Cocaine-Related Disorders
Conditions
Keywords
Cocaine dependence, treatment, memantine
Brief summary
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.
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.
Interventions
DRUGMemantine
Memantine
DRUGplacebo
placebo
Sponsors
National Institute on Drug Abuse (NIDA)
Research Foundation for Mental Hygiene, Inc.
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weekly Cocaine Use | weekly use during length of study participation | Mean number of cocaine using days per week based on self reported use verified by cocaine toxicology results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Abstinence Based on Daily Self Reported Cocaine Use | reported weekly cocaine use for 12 weeks/ or study participation | 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; |
Countries
United States
Participant flow
Recruitment details
Individuals who applied for treatment at Columbia University's Substance Treatment and Research Service (STARS) outpatient clinic in New York City, USA, were recruited for this study. The study recruited from March 2003-February 2007.
Pre-assignment details
patients entered a 2-week, single-blind placebo lead-in period. To be eligible for randomization, patients were required to attend at least 2 of 4 scheduled therapy sessions and to submit at least 4 of 6 scheduled urine samples during the two weeks of the lead-in period.
Participants by arm
| Arm | Count |
|---|---|
| Memantine Memantine 40mg/day | 39 |
| Placebo Placebo daily dose | 42 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | discontinued intervention | 12 | 10 |
| Overall Study | Lost to Follow-up | 5 | 5 |
Baseline characteristics
| Characteristic | Placebo | Memantine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 39 Participants | 81 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 9 | 40 years STANDARD_DEVIATION 7 | 40 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 42 participants | 39 participants | 81 participants |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 33 Participants | 31 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 39 | 28 / 42 |
| serious Total, serious adverse events | 0 / 39 | 2 / 42 |
Outcome results
Primary
Weekly Cocaine Use
Mean number of cocaine using days per week based on self reported use verified by cocaine toxicology results.
Time frame: weekly use during length of study participation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Weekly Cocaine Use | 1.1 days | Standard Deviation 1.9 |
| Placebo | Weekly Cocaine Use | 1.3 days | Standard Deviation 1.8 |
Secondary
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;
Time frame: reported weekly cocaine use for 12 weeks/ or study participation
Population: All analyses were performed on an intent-to-treat basis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Memantine | Cocaine Abstinence Based on Daily Self Reported Cocaine Use | 15 participants |
| Placebo | Cocaine Abstinence Based on Daily Self Reported Cocaine Use | 13 participants |