Memantine as a Supplement to Naltrexone in Treating Heroin Dependence (NAMHS)

Placebo Controlled Study of Memantine as an Adjunct to Naltrexone in the Treatment of Opioid Dependence

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.

Study Overview

• Status: Completed
• Conditions: Heroin Dependence; Opioid Dependence
• Intervention / Treatment: Drug: Vivitrol; Drug: memantine

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 Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • STARS

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:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

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

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Adam Bisaga, MD, Columbia University

Publications and helpful links

General Publications

• Bisaga A, Sullivan MA, Cheng WY, Carpenter KM, Mariani JJ, Levin FR, Raby WN, Nunes EV. A placebo controlled trial of memantine as an adjunct to oral naltrexone for opioid dependence. Drug Alcohol Depend. 2011 Dec 1;119(1-2):e23-9. doi: 10.1016/j.drugalcdep.2011.05.019. Epub 2011 Jun 28.

Helpful Links

• stars website

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: May 17, 2007
• First Submitted That Met QC Criteria: May 18, 2007
• First Posted (Estimate): May 21, 2007

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: June 19, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: opioid dependence; naltrexone; memantine; heroin abuse; opiate abuse
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Heroin Dependence; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Narcotic Antagonists; Alcohol Deterrents; Antiparkinson Agents; Anti-Dyskinesia Agents; Naltrexone; Memantine
• Other Study ID Numbers: #5936R R01 DA015822-01; R01DA015822 (U.S. NIH Grant/Contract)