Memantine-enhanced Buprenorphine Treatment for Opioid-dependent Young Adults

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.

Study Overview

• Status: Completed
• Conditions: Opioid Dependence
• Intervention / Treatment: Drug: Memantine; Drug: Memantine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Memantine 30mg/day + Buprenorphine; 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.	Drug: Memantine; 30mg/day Memantine orally everyday for 12 weeks; Drug: Memantine; 15 mg/day Memantine orally everyday for 12 weeks
EXPERIMENTAL: Memantine 15mg/day + Buprenorphine; 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.	Drug: Memantine; 30mg/day Memantine orally everyday for 12 weeks; Drug: Memantine; 15 mg/day Memantine orally everyday for 12 weeks
PLACEBO_COMPARATOR: Memantine 0mg/day + Buprenorphine; 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.	Drug: Placebo; Placebo orally everyday for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Opioid Use 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.	Weekly from week 1 to 13
Number of Participants Who Were Estimated to Have Survived as Assessed by Survival Curve of Relapse Rate After Achieving Complete Abstinence on Week 8	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.	Weeks after buprenorphine discontinuation week 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Retention	Treatment retention during the stabilization period weeks 1 to 8 and after buprenorphine / naloxone discontinuation weeks 9 to 13.	Weekly

Collaborators and Investigators

• Sponsor: University of Massachusetts, Worcester
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Gerardo Gonzalez, M.D., University of Massachusetts, Worcester

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: January 18, 2010
• First Submitted That Met QC Criteria: January 19, 2010
• First Posted (ESTIMATE): January 20, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 1, 2015
• Last Update Submitted That Met QC Criteria: March 11, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Drug Abuse
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: H-13261; 1R01DA027138-01 (NIH)