NAMHS: Memantine as a Supplement to Naltrexone in Treating Heroin Dependence

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00476242
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 82
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

Prospective participants will undergo a screening process at the clinic to determine eligibility. After screening, eligible patients will complete an 8-day inpatient detoxification, followed by a 12-week outpatient phase. Patients will be randomly assigned to one of two conditions (1) Naltrexone + Placebo; (2) Naltrexone + Memantine 20 mg bid. Long-acting, injectable form of naltrexone (Vivitrol) will be administered once per month (the total of three injections) while memantine or placebo will be taken daily. In addition, patients will receive twice weekly psychosocial intervention that will include motivational interviewing and cognitive-behavioral relapse prevention. The outpatient treatment will also consist of 3 weekly visits to the clinic in which patients will receive counseling to help maintain abstinence and improve compliance with study medication.

Condition or Disease	Intervention/Treatment	Phase
Opioid Dependence; Heroin Dependence	Drug: Vivitrol; Drug: memantine	Phase 2/Phase 3

Detailed Description

In the proposed trial heroin-dependent patients undergoing detoxification will be randomly assigned to one of two conditions (1) Naltrexone + Placebo; (2) Naltrexone + Memantine 20 mg bid. Long-acting, injectable form of naltrexone (Vivitrol) will be administered once per month (the total of three injections) while memantine or placebo will be taken daily. In addition, patients will receive twice weekly psychosocial intervention that will include motivational interviewing and cognitive-behavioral relapse prevention. The goal of psychosocial intervention is to improve compliance with medication and maintain abstinence. A double-blind trial will last twelve weeks with assessments at baseline and at each appointment three times per week. After the completion of a double-blind study (experimental phase), participants will continue open label treatment with Vivitrol and therapy for additional three months (study extension phase). Repeated assessments will also be completed one, two, and three months following the end of double-blind treatment. For the experimental phase of the study, the primary aim is to test the efficacy of memantine in reducing early attrition and improving outcome in opioid-dependent individuals maintained on naltrexone and primary outcome measures will be retention in treatment by the end of the study and heroin abstinence.

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Placebo Controlled Study of Memantine as an Adjunct to Naltrexone in the Treatment of Opioid Dependence
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Memantine and Vivitrol intramuscular injection of Vivitrol 380 mg and 20 mg bid Memantine (PO)	Drug: Vivitrol; intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections); Other Names: intramuscular injection of Vivitrol 380 mg ; Drug: memantine; Memantine will be given in two divided doses, starting with the second day of the naltrexone induction, with the target doses of 40 mg/day (or the maximum tolerated dose), for a total of twelve weeks of medication treatment.
Placebo Comparator: Placebo and Vivitrol intramuscular injection of Vivitrol 380 mg and Placebo	Drug: Vivitrol; intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections); Other Names: intramuscular injection of Vivitrol 380 mg

Outcome Measures

Primary Outcome Measures

1. Opiate Use Measured by Urine Toxicology Results [3x/week during 12 weeks of the trial or study participation]

   Opiate use was qualified by the number of opiate positive urine results.

2. Retention in Treatment The Primary Outcome Measure Will be the Dichotomous Measure Retention in Treatment (Whether the Patient Completes the 12 Week Trial, Yes/no). [Week 12]

Secondary Outcome Measures

1. Opiate Craving Based on Heroin Craving Scale [Average of twice weekly assessments for 12 weeks of study or length of participation]

   Range 0- 100 ( 0= no craving; 100= very strong craving

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult, aged 18-60.

2. Meets Diagnostic and Statistical Manual IV (DSM-IV) criteria for current opiate dependence disorder of at least six months duration, supported by a positive urine for opiates and a positive naloxone challenge test if the diagnosis is unclear.

3. Able to give informed consent.

Exclusion Criteria:

1. Pregnancy, lactation, or failure in a sexually active woman to use adequate contraceptive methods.

2. Active medical illness which might make participation hazardous, such as untreated hypertension, acute hepatitis with serum glutamic oxaloacetic transaminase or serum glutamic-pyruvic transaminase levels >2 times normal, unstable diabetes, chronic organic mental disorder (e.g., AIDS dementia).

3. Active psychiatric disorder which might interfere with participation or make participation hazardous, including DSM-IV schizophrenia, bipolar disorder with mania or psychosis, and depressive disorder with suicide risk or 1 or more suicide attempts within the past year.

4. History of allergic reaction to buprenorphine, naloxone, memantine, naltrexone, clonidine, or clonazepam.

5. Currently prescribed or regularly taking opiates for chronic pain or medical illness.

6. Current participation in another intensive psychotherapy or substance abuse treatment program or currently prescribed psychotropic medications.

7. Current participation in a methadone maintenance treatment program and/or regular use of illicit methadone (>30 mg per week).

8. History of accidental drug overdose in the last three years or any other significant history of overdose following detoxification defined as an episode of opioid-induced unconsciousness or incapacitation, whether or not medical treatment was sought or received.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	STARS	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Adam Bisaga, MD, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• stars website

Publications

None provided.

• Responsible Party: Adam Bisaga, Research Psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT00476242
• Other Study ID Numbers: #5936R R01 DA015822-01; R01DA015822; NCT00126711
• First Posted: May 21, 2007
• Last Update Posted: Jul 17, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by Adam Bisaga, Research Psychiatrist, New York State Psychiatric Institute: heroin abuse; opiate abuse; opioid dependence; naltrexone; memantine
• Additional relevant MeSH terms: Opioid-Related Disorders; Heroin Dependence; Naltrexone; Memantine

Study Results

Participant Flow

Pre-assignment Detail	27 participants dropped during the inpatient detoxification, therefore only 55 participants were randomized out of the 82 total enrolled.

Arm/Group Title	Placebo and Vivitrol	Memantine and Vivitrol
Arm/Group Description	Participants treated with placebo capsules and Vivitrol.	Participants treated with memantine 40 mg/d capsules and Vivitrol.
Period Title: Overall Study
STARTED	27	28
COMPLETED	19	12
NOT COMPLETED	8	16

Baseline Characteristics

Arm/Group Title	Memantine and Vivitrol	Placebo and Vivitrol	Total
Arm/Group Description	intramuscular injection of Vivitrol 380 mg and 20 mg bid Memantine (PO) Vivitrol: intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections) memantine: Memantine will be given in two divided doses, starting with the second day of the naltrexone induction, with the target doses of 40 mg/day (or the maximum tolerated dose), for a total of twelve weeks of medication treatment.	intramuscular injection of Vivitrol 380 mg and Placebo Vivitrol: intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections)	Total of all reporting groups
Overall Participants	28	27	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.7 (12.0)	39.0 (11.5)	39.4 (11.5)
Sex: Female, Male (Count of Participants)
Female	4 14.3%	7 25.9%	11 20%
Male	24 85.7%	20 74.1%	44 80%
Region of Enrollment (participants) [Number]
United States	28 100%	27 100%	55 100%

Outcome Measures

1. Primary Outcome

Title	Opiate Use Measured by Urine Toxicology Results
Description	Opiate use was qualified by the number of opiate positive urine results.
Time Frame	3x/week during 12 weeks of the trial or study participation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Memantine and Vivitrol	Placebo and Vivitrol
Arm/Group Description	intramuscular injection of Vivitrol 380 mg and 20 mg bid Memantine (PO) Vivitrol: intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections) memantine: Memantine will be given in two divided doses, starting with the second day of the naltrexone induction, with the target doses of 40 mg/day (or the maximum tolerated dose), for a total of twelve weeks of medication treatment.	intramuscular injection of Vivitrol 380 mg and Placebo Vivitrol: intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections)
Measure Participants	28	27
Median (Inter-Quartile Range) [Percent of total urine samples]	9	10

2. Primary Outcome

Title	Retention in Treatment The Primary Outcome Measure Will be the Dichotomous Measure Retention in Treatment (Whether the Patient Completes the 12 Week Trial, Yes/no).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Memantine and Vivitrol	Placebo and Vivitrol
Arm/Group Description	intramuscular injection of Vivitrol 380 mg and 20 mg bid Memantine (PO) Vivitrol: intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections) memantine: Memantine will be given in two divided doses, starting with the second day of the naltrexone induction, with the target doses of 40 mg/day (or the maximum tolerated dose), for a total of twelve weeks of medication treatment.	intramuscular injection of Vivitrol 380 mg and Placebo Vivitrol: intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections)
Measure Participants	28	27
Number [participants]	12 42.9%	19 70.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Memantine and Vivitrol, Placebo and Vivitrol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.047
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Opiate Craving Based on Heroin Craving Scale
Description	Range 0- 100 ( 0= no craving; 100= very strong craving
Time Frame	Average of twice weekly assessments for 12 weeks of study or length of participation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo and Vivitrol	Memantine and Vivitrol
Arm/Group Description	Participants treated with placebo capsules and Vivitrol.	Participants treated with memantine 40 mg/d capsules and Vivitrol.
Measure Participants	27	28
Mean (Standard Deviation) [units on a scale]	18.47 (25.79)	15.74 (22.22)

Adverse Events

Arm/Group Title	Memantine and Vivitrol		Placebo and Vivitrol
Arm/Group Description	intramuscular injection of Vivitrol 380 mg and 20 mg bid Memantine (PO) Vivitrol: intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections) memantine: Memantine will be given in two divided doses, starting with the second day of the naltrexone induction, with the target doses of 40 mg/day (or the maximum tolerated dose), for a total of twelve weeks of medication treatment.		intramuscular injection of Vivitrol 380 mg and Placebo Vivitrol: intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections)
All Cause Mortality
	Memantine and Vivitrol		Placebo and Vivitrol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Memantine and Vivitrol		Placebo and Vivitrol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/28 (3.6%)		0/27 (0%)
Psychiatric disorders
Psychiatric worsening	1/28 (3.6%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Memantine and Vivitrol		Placebo and Vivitrol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/28 (71.4%)		17/27 (63%)
Psychiatric disorders
Insomnia	17/28 (60.7%)	17	13/27 (48.1%)	13
Mood changes	7/28 (25%)	7	9/27 (33.3%)	9
Increased/decreased appetite	6/28 (21.4%)	6	5/27 (18.5%)	5
Fatigue/drowsiness	7/28 (25%)	7	8/27 (29.6%)	8
Nausea/Vomiting	1/28 (3.6%)	1	4/27 (14.8%)	4
Diarrhea	7/28 (25%)	7	3/27 (11.1%)	3
Headache	2/28 (7.1%)	2	4/27 (14.8%)	4
Body Aches	4/28 (14.3%)	4	6/27 (22.2%)	6
GI Distress	4/28 (14.3%)	4	7/27 (25.9%)	7
Sweating/chills	2/28 (7.1%)	2	5/27 (18.5%)	5
Faintness/dizziness	2/28 (7.1%)	2	3/27 (11.1%)	3

Limitations/Caveats

[Not Specified]

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.