Memantine-enhanced Buprenorphine Treatment for Opioid-dependent Young Adults

Phase 2

Completed

Conditions: Opioid Dependence

Interventions: Drug: Memantine
Drug: Placebo

Registration Number: NCT01052662

Lead Sponsor: University of Massachusetts, Worcester

Brief Summary: The purpose of this study is to examine the effect of memantine and buprenorphine on opioid abusing behavior, to determine the effect of memantine and buprenorphine on early relapse and to evaluate the tolerability of memantine co-administrated with buprenorphine. The study seeks to determine if combined treatment of memantine and buprenorphine may provide shorter-term treatment for opioid dependence.

Detailed Description: Opiate dependence is an increasing problem among young adults (18-25 years old) whose rates of current use of illicit drugs are generally high (19.7 %)according to data from the 2007 National Survey on Drug Use \& Health (Substance Abuse and Mental Health Services Administration 2008). Young adults start using heroin around this age range, and more recently have had increasing rates of prescription-type drug use. Given that young adults with opiate dependence who are seeking treatment are relatively treatment naïve, have a shorter period of addiction, and are more likely to choose buprenorphine over methadone, developing short-term buprenorphine treatment alternatives to long-term methadone agonist treatment is needed.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 87

Inclusion Criteria

Men and women between 18-25 years old
Opioid dependence as evidenced by signs of opiate withdrawal, self-reported history of opioid dependence for a consecutive 12 month period and positive urine for opioids

Exclusion Criteria

Current diagnosis of other drug or alcohol dependence (other than opiates, cannabis or tobacco)
Serious medical illness (e.g. major cardiovascular, renal, endocrine, hepatic disorder)
Current serious psychiatric illness or history of psychosis, schizophrenia, bipolar type I disorder and participants with suicidal or homicidal thoughts
Women who are pregnant, nursing or refuse to use a reliable form of birth control or refuse monthly pregnancy testing
Screening liver function tests (SGOT or SGPT) greater than 3 times normal

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Memantine 30mg/day + Buprenorphine	Memantine	Participants were inducted onto buprenorphine/naloxone sublingual tablets during the first week of study participation. The dose was titrated from bup/nal 8mg to bup/nal 16mg in three days where it will remain until the last day of week 8. The 7-day discontinuation of buprenorphine-naloxone on week 9 was 12mg, 10mg, 8mg, 6mg, 4mg, 2mg, 2mg and stopped. Memantine 5mg in the morning was started on week 2. The dose was titrated on a twice a day schedule until the target dose of 30 mg/day was achieved by week 4. The medication was discontinued over a one-week period on week 13. Patients received a 7-day supply of their medication each week.
Memantine 0mg/day + Buprenorphine	Placebo	Participants were inducted onto buprenorphine/naloxone sublingual tablets during the first week of study participation. The dose was titrated from bup/nal 8mg to bup/nal 16mg in three days where it will remain until the last day of week 8. The 7-day discontinuation of buprenorphine-naloxone on week 9 was 12mg, 10mg, 8mg, 6mg, 4mg, 2mg, 2mg and stopped. Matching placebo capsule was started on week 2. The placebo capsules were given on a twice a day schedule until week 12 and then discontinued over a one-week period on week 13. Patients received a 7-day supply of their medication each week.
Memantine 15mg/day + Buprenorphine	Memantine	Participants were inducted onto buprenorphine/naloxone sublingual tablets during the first week of study participation. The dose was titrated from bup/nal 8mg to bup/nal 16mg in three days where it will remain until the last day of week 8. The 7-day discontinuation of buprenorphine-naloxone on week 9 was 12mg, 10mg, 8mg, 6mg, 4mg, 2mg, 2mg and stopped. Memantine 5mg in the morning was started on week 2. The dose was titrated on a twice a day schedule until the target dose of 15 mg/day was achieved by week 4. The medication was discontinued over a one-week period on week 13. Patients received a 7-day supply of their medication each week.

Primary Outcome Measures

Name	Time	Method
Change of Opioid Use From Week 1 to 13	Weekly from week 1 to 13	The primary outcome variable was the change from baseline of the mean proportion of weekly opioid use assessed by self-reported days of use and/or positive urine drug screen during the previous week using the time-line followed-back method (TLFB) . A positive urine counted as 1, as did each self-reported day of use. Each participants total was divided by 8. Mean proportion by group were calculated by averaging the proportions across participants in that group.
Number of Participants Who Were Estimated to Have Survived as Assessed by Survival Curve of Relapse Rate After Achieving Complete Abstinence on Week 8	Weeks after buprenorphine discontinuation week 9	Calculated survival curve from abstinence in Week 8 to first positive opioid urine screen or first reported relapse to opioid use to evaluate the effect of memantine on reducing early relapse and after rapid buprenorphine discontinuation on week 9. The last observation carried forward (LOCF) was used to perform our event survival analyses.

Secondary Outcome Measures

Name	Time	Method
Treatment Retention	Weekly	Treatment retention during the stabilization period weeks 1 to 8 and after buprenorphine / naloxone discontinuation weeks 9 to 13.