Memantine as a Supplement to Naltrexone in Treating Heroin Dependence - Full Text View

Sponsor:	New York State Psychiatric Institute
Collaborator:	National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):	Adam Bisaga, National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier:	NCT00476242

Purpose

Free treatment for heroin or opiate abuse. Research study involves inpatient detox and outpatient care.

The number of new heroin users and problems associated with heroin use has increased steadily over the past several years. While methadone maintenance remains the most effective treatment for opioid dependence, it has several limitations and is controversial.

Naltrexone maintenance is an alternate treatment for opiate dependence that is promising, but currently has limited usefulness due to poor patient compliance and low patient acceptability. There is strong support from animal research that another class of drugs, NMDA-R antagonists, may also be an effective treatment for opiate dependence. In laboratory animals, NMDA-R antagonists have inhibited behaviors associated with relapse, reduced opiate self-administration, and helped with withdrawal symptoms. In humans, NMDA-R antagonists have reduced signs and symptoms associated with opiate withdrawal and reduced heroin craving. The primary aim of this study is to determine the efficacy of memantine as an adjunct to naltrexone maintenance in detoxified heroin-dependent individuals.

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.

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 in the final four weeks prior to study endpoint. For the extension phase of the study, primary aim is to assess the long-term safety and efficacy of Vivitrol in preventing relapse to drug use and its effects on quality-of-life measures.

Condition	Intervention	Phase
Opioid Dependence Heroin Dependence	Drug: naltrexone Drug: memantine	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Memantine and Naltrexone Treatment for Opioid Dependence

Resource links provided by NLM:

MedlinePlus related topics: Heroin

Drug Information available for: Naltrexone Naltrexone hydrochloride Memantine Memantine hydrochloride

U.S. FDA Resources

Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:

Opiate use measured by urine toxicology results [ Time Frame: 3x/week during 12 weeks of the trial or study participation ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

opiate craving based on Heroin craving scale [ Time Frame: measured daily for 12 weeks of study or length of participation ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	June 2005
Study Completion Date:	August 2011
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 intramuscular injection of Vivitrol 380 mg and 20 mg bid Memantine (PO)	Drug: naltrexone intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections) Other Name: 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: 2 intramuscular injection of Vivitrol 380 mg and Placebo	Drug: naltrexone intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections) Other Name: intramuscular injection of Vivitrol 380 mg

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult, aged 18-60.
Meets 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.
Able to give informed consent.

Exclusion Criteria:

Pregnancy, lactation, or failure in a sexually active woman to use adequate contraceptive methods.
Active medical illness which might make participation hazardous, such as untreated hypertension, acute hepatitis with SGOT or SGPT levels >2 times normal, unstable diabetes, chronic organic mental disorder (e.g., AIDS dementia).
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.
History of allergic reaction to buprenorphine, naloxone, memantine, naltrexone, clonidine, or clonazepam.
Currently prescribed or regularly taking opiates for chronic pain or medical illness.
Current participation in another intensive psychotherapy or substance abuse treatment program or currently prescribed psychotropic medications.
Current participation in a methadone maintenance treatment program and/or regular use of illicit methadone (>30 mg per week).
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00476242

Locations

United States, New York
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

More Information

No publications provided

Responsible Party:	Adam Bisaga, Associate professor of clinical psychiatry, National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier:	NCT00476242 History of Changes
Obsolete Identifiers:	NCT00126711
Other Study ID Numbers:	R01 DA015822-01, R01DA015822, DPMCDA
Study First Received:	May 17, 2007
Last Updated:	October 17, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by New York State Psychiatric Institute:

heroin abuse
opiate abuse
opioid dependence
naltrexone
memantine

Additional relevant MeSH terms:

Heroin Dependence
Opioid-Related Disorders
Substance-Related Disorders
Mental Disorders
Naltrexone
Memantine
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents

Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents

ClinicalTrials.gov processed this record on February 09, 2012