Opioid Dependence, Heroin Dependence
Conditions
Keywords
heroin abuse, opiate abuse, opioid dependence, naltrexone, memantine
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.
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.
Interventions
DRUGVivitrol
intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections)
DRUGmemantine
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.
Sponsors
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Pre-assignment details
27 participants dropped during the inpatient detoxification, therefore only 55 participants were randomized out of the 82 total enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Memantine and Vivitrol 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. | 28 |
| Placebo and Vivitrol intramuscular injection of Vivitrol 380 mg and Placebo
Vivitrol: intramuscular injection of Vivitrol 380 mg for up to 6 months (six injections) | 27 |
| Total | 55 |
Baseline characteristics
| Characteristic | Memantine and Vivitrol | Placebo and Vivitrol | Total |
|---|---|---|---|
| Age, Continuous | 39.7 years STANDARD_DEVIATION 12 | 39.0 years STANDARD_DEVIATION 11.5 | 39.4 years STANDARD_DEVIATION 11.5 |
| Region of Enrollment United States | 28 participants | 27 participants | 55 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 24 Participants | 20 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 28 | 17 / 27 |
| serious Total, serious adverse events | 1 / 28 | 0 / 27 |
Outcome results
Primary
Opiate Use Measured by Urine Toxicology Results
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Memantine and Vivitrol | Opiate Use Measured by Urine Toxicology Results | 9 Percent of total urine samples |
| Placebo and Vivitrol | Opiate Use Measured by Urine Toxicology Results | 10 Percent of total urine samples |
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Memantine and Vivitrol | 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). | 12 participants |
| Placebo and Vivitrol | 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). | 19 participants |
p-value: 0.047Log Rank
Secondary
Opiate Craving Based on Heroin Craving Scale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine and Vivitrol | Opiate Craving Based on Heroin Craving Scale | 18.47 units on a scale | Standard Deviation 25.79 |
| Placebo and Vivitrol | Opiate Craving Based on Heroin Craving Scale | 15.74 units on a scale | Standard Deviation 22.22 |