Memantine-enhanced Buprenorphine Treatment for Opioid-dependent Young Adults

NCT01052662 | Completed Phase 2 Results DMC

• 2 other identifiers: H-132611R01DA027138-01
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid Dependence

Keywords

Drug Abuse

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Treatment Retention

  Weekly

Study Arms (3)

Memantine 30mg/day + Buprenorphine

EXPERIMENTAL

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

Memantine 15mg/day + Buprenorphine

EXPERIMENTAL

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

Memantine 0mg/day + Buprenorphine

PLACEBO COMPARATOR

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

Interventions

Memantine DRUG

30mg/day Memantine orally everyday for 12 weeks

Memantine 30mg/day + Buprenorphine

Placebo DRUG

Placebo orally everyday for 12 weeks

Memantine 0mg/day + Buprenorphine

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

University of Massachusetts Medical School

Worcester, Massachusetts, 01605, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Substance-Related Disorders

Interventions

Memantine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Rapid discontinuation of buprenorphine was associated with dropout that may have limited the statistical power to evaluate some variables. Memantine for 7 weeks may have been too short, and a longer exposure may have yielded better results.

Results Point of Contact

• Title: Gerardo Gonzalez, MD
• Organization: University of Massachusetts Medical School

gerardo.gonzalez@umassmed.edu

508 856 6480

Study Officials

• Gerardo Gonzalez, M.D.

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 18, 2010
• First Posted: January 20, 2010
• Study Start: October 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: October 1, 2013
• Last Updated: April 1, 2015
• Results First Posted: March 6, 2015

Record last verified: 2015-03

Locations

US (1)