Effectiveness of Memantine in Treating Cocaine-Dependent Individuals - 2

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00134901
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH), Research Foundation for Mental Hygiene, Inc. (Other)
• Enrollment: 81
• Location: 1
• Arms: 2
• Duration (Months): 50
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cocaine-Related Disorders	Drug: Memantine; Drug: placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled Trial of the Effectiveness of Memantine in Treating Cocaine Dependence
• Study Start Date: Mar 1, 2003
• Actual Primary Completion Date: May 1, 2007
• Actual Study Completion Date: May 1, 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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;

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Foundation for Mental Hygiene, Inc.	New York	New York	United States	10032

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Frances R Levin, M.D., Research Foundation for Mental Hygiene, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Substance Treatment and Abuse Research Service (STARS)

Publications

None provided.

• Responsible Party: Frances R Levin, Director of Substance Use Disorder, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT00134901
• Other Study ID Numbers: #4496-NIDA-12761-2; P50DA012761
• First Posted: Aug 25, 2005
• Last Update Posted: Apr 24, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Frances R Levin, Director of Substance Use Disorder, New York State Psychiatric Institute: Cocaine dependence; treatment; memantine
• Additional relevant MeSH terms: Cocaine-Related Disorders; Memantine

Study Results

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 Detail	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.

Arm/Group Title	Memantine	Placebo
Arm/Group Description	Memantine 40mg/day	Placebo daily dose
Period Title: Overall Study
STARTED	39	42
COMPLETED	22	27
NOT COMPLETED	17	15

Baseline Characteristics

Arm/Group Title	Memantine	Placebo	Total
Arm/Group Description	Memantine 40mg/day	Placebo daily dose	Total of all reporting groups
Overall Participants	39	42	81
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	39 100%	42 100%	81 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40 (7)	40 (9)	40 (8)
Sex: Female, Male (Count of Participants)
Female	8 20.5%	9 21.4%	17 21%
Male	31 79.5%	33 78.6%	64 79%
Region of Enrollment (participants) [Number]
United States	39 100%	42 100%	81 100%

Outcome Measures

1. Secondary Outcome

Title	Cocaine Abstinence Based on Daily Self Reported Cocaine Use
Description	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

Outcome Measure Data

Analysis Population Description

All analyses were performed on an intent-to-treat basis

Arm/Group Title	Memantine	Placebo
Arm/Group Description	Memantine 40mg/day	Placebo daily dose
Measure Participants	39	42
Number [participants]	15 38.5%	13 31%

2. Primary Outcome

Title	Weekly Cocaine Use
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Memantine	Placebo
Arm/Group Description	Memantine Memantine: Memantine	Placebo placebo: placebo
Measure Participants	39	42
Mean (Standard Deviation) [days]	1.1 (1.9)	1.3 (1.8)

Adverse Events

Arm/Group Title	Memantine		Placebo
Arm/Group Description	Memantine 40mg/day		Placebo daily dose
All Cause Mortality
	Memantine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Memantine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		2/42 (4.8%)
Gastrointestinal disorders
abdominal pain	0/39 (0%)	0	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
finger fracture	0/39 (0%)	0	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Memantine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/39 (61.5%)		28/42 (66.7%)
Gastrointestinal disorders
GI upset	2/39 (5.1%)	2	2/42 (4.8%)	2
nausea	2/39 (5.1%)	2	2/42 (4.8%)	2
diarrhea	2/39 (5.1%)	2	0/42 (0%)	0
General disorders
insomnia	3/39 (7.7%)	3	6/42 (14.3%)	6
chills	0/39 (0%)	0	3/42 (7.1%)	3
fever	0/39 (0%)	0	3/42 (7.1%)	3
light headed	4/39 (10.3%)	4	3/42 (7.1%)	3
drowsiness	3/39 (7.7%)	3	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
muscle aches	2/39 (5.1%)	2	5/42 (11.9%)	5
back ache	3/39 (7.7%)	3	2/42 (4.8%)	2
Nervous system disorders
headache	5/39 (12.8%)	5	7/42 (16.7%)	7
Psychiatric disorders
anxiety	2/39 (5.1%)	2	2/42 (4.8%)	2
Skin and subcutaneous tissue disorders
rash	2/39 (5.1%)	2	1/42 (2.4%)	1

Limitations/Caveats

participants who had achieved abstinence during the lead-in remained abstinent throughout the trial and there was little relapse-like behavior for a medication to address.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.