Memantine as a Supplement to Naltrexone in Treating Heroin Dependence

Official Title: “Memantine and Naltrexone Treatment for Opioid Dependence”

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.

Intervention(s) in this Clinical Trial

• Drug: naltrexone
  • intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections)
• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • intramuscular injection of Vivitrol 380 mg and 20 mg bid Memantine (PO)
• Placebo Comparator: 2
  • intramuscular injection of Vivitrol 380 mg and Placebo

Primary Measures

• Opiate use measured by urine toxicology results
  • Time Frame: 3x/week during 12 weeks of the trial or study participation
    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
    Safety Issue?: No

Secondary Measures

• opiate craving based on Heroin craving scale
  • Time Frame: measured daily for 12 weeks of study or length of participation
    Safety Issue?: No

Inclusion Criteria:

• 1. Adult, aged 18-60.
• 2. 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.
• 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 SGOT or SGPT 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: New York State Psychiatric Institute Other

Overall Clinical Trial Officials and Contacts

Adam Bisaga, MD Principal Investigator Columbia University  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00476242

Study ID Number: R01 DA015822-01

ClinicalTrials.gov Identifier: NCT00476242

Health Authority: United States: Food and Drug Administration