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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01DA027138-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Memantine | Drug | 30mg/day Memantine orally everyday for 12 weeks |
| |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gerardo Gonzalez, M.D. | University of Massachusetts, Worcester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Massachusetts Medical School | Worcester | Massachusetts | 01605 | United States |
229 individuals of the 354 persons who were interested in the study were assessed not eligible to participate. Of the 125 subjects that were screen over one week, only 87 subjects meet criteria for study participation. Reason for exclusion included: declined (N=22), psychiatric (N=6), other SUD (N=6), abnormal labs (N=3) and medical reason (N=1)
Recruitment was done by newspaper advertising, referrals from the University of Massachusetts Addiction and Comorbidity Treatment Service (ACTS) and from community-based substance abuse clinics.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Memantine: 30mg/day Memantine orally everyday for 12 weeks |
| FG001 | 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. Memantine: 15 mg/day Memantine orally everyday for 12 weeks |
| FG002 | 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. Placebo: Placebo orally everyday for 12 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-treat sample
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Memantine: 30mg/day Memantine orally everyday for 12 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 80 subjects intent-to-treat. | Posted | Mean | Standard Error | Mean Proportion of Opioid Use in Week 13 | Weekly from week 1 to 13 |
|
Adverse events were collected from week 1 to week 13.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Memantine: 30mg/day Memantine orally everyday for 12 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain | Nervous system disorders | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gerardo Gonzalez, MD | University of Massachusetts Medical School | 508 856 6480 | gerardo.gonzalez@umassmed.edu |
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| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| D019966 | Substance-Related Disorders |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D008559 | Memantine |
| ID | Term |
|---|---|
| D000547 | Amantadine |
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
| D006844 | Hydrocarbons, Cyclic |
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|
| Memantine |
| Drug |
15 mg/day Memantine orally everyday for 12 weeks |
|
| Placebo | Drug | Placebo orally everyday for 12 weeks |
|
| Pharmacy issue |
|
| Adverse Event |
|
| Legal Problem |
|
| Administrative |
|
| BG001 | 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. Memantine: 15 mg/day Memantine orally everyday for 12 weeks |
| BG002 | 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. Placebo: Placebo orally everyday for 12 weeks |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
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| Opioid use | Number | participants |
|
| Years of opioid use | Mean | Standard Deviation | years |
|
| Severity of Dependence Scale | Performed at screening, we used this scale for urn randomization based on the severity of opiate dependence score. This instrument has 5 questions that are scored on a four-point scale from 0 ( never/almost never or not difficult) to 3 (always/nearly always or impossible). Overall scores range from 0 to 15, with scores above 10 indicating high severity. | Mean | Standard Deviation | units on a scale |
|
| Clinical Opiate Withdrawal Scale (COWS) | The COWS is an 11-item interviewer administered questionnaire designed to provide a description of signs and symptoms of opiate withdrawal that can be observed directly in the participant (e.g., sweating, runny nose, etc). Scores range from 0 to 36. Score 5-12 = Mild, 13-24 = Moderate, 25-36 = Moderately Severe and more than 36 = Severe Withdrawal. | Mean | Standard Deviation | units on a scale |
|
| Heroin Craving Questionnaire - Short Form 14 (HCQ-SF-14) | The Heroin Craving Questionnaire - Short Form 14 (HCQ-SF-14) consists of 14 statements about the respondent's feelings and thoughts about using heroin as he or she is completing the questionnaire (i.e., right now). This instrument obtains a reflection of the respondent's general heroin craving. This instrument was modified to include craving for prescription opioids. Each item is scored on a scale ranging from 1 for "Strongly Disagree" to 7 for "Strongly Agree." The total score is the average of the sum all 14 items with range from 1 to 7 with higher score indicating worse craving. | Mean | Standard Deviation | units on a scale |
|
| Center for Epidemiologic Studies Depression scale (CES-D) | CES-D is a 20-item self-report measure of depressive symptoms. CES-D was administered at intake and weekly. The range of scores is from 0 to 60, with higher scores reflecting increased depressive symptoms. The CES-D does not heavily depend on pathological items or somatic symptoms compared with other scales. | Mean | Standard Deviation | units on a scale |
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| Barratt Impulsivity Questionnaire | The Barratt Impulsivity Questionnaire is a brief, participant-administered 30-item, self-rating scale where participants answer questions regarding behavior and planning using a four-point scale (1= Rarely/Never, 2= Occasionally, 3= Often, 4= Almost always/Always) where the maximum overall impulsivity score is 120 indicating more impulsive and the minimum score is 30. | Mean | Standard Deviation | units on a scale |
|
| Inhibitory Control (mean % error) | Antisaccade Task: Participants view a computer screen displaying two placeholder outline boxes on either side of a fixation cross. Subjects are instructed to look away from the go signal when it appears inside one of the placeholder boxes. For each trial, the first saccade that follows the go signal will be labeled an impulsivity error (i.e., a prosaccade) if it lands on the box containing the go signal and a correct response (i.e., an antisaccade) if it lands in the goal box. This task is an excellent measure of the control over impulsive behavior with higher scores indicating worse control. | Mean | Standard Deviation | mean percentage of error (prosaccade) |
|
| OG001 | 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. Memantine: 15 mg/day Memantine orally everyday for 12 weeks |
| OG002 | 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. Placebo: Placebo orally everyday for 12 weeks |
|
|
|
| Secondary | Treatment Retention | Treatment retention during the stabilization period weeks 1 to 8 and after buprenorphine / naloxone discontinuation weeks 9 to 13. | Intent-treat-sample (ITT) that was inducted onto buprenorphine / naloxone and received one dose of study medication on week 2. | Posted | Mean | 95% Confidence Interval | weeks in treatment | Weekly |
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|
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| Primary | 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. | Participants that achieved complete abstinence by self-report that was confirmed with negative urine toxicology at week 8. | Posted | Number | participants | Weeks after buprenorphine discontinuation week 9 |
|
|
|
|
| 0 |
| 27 |
| 18 |
| 27 |
| EG001 | 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. Memantine: 15 mg/day Memantine orally everyday for 12 weeks | 0 | 24 | 15 | 24 |
| EG002 | 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. Placebo: Placebo orally everyday for 12 weeks | 0 | 29 | 23 | 29 |
| Upper Respiratory Intection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vivid Dreams | Psychiatric disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Drowsiness | Nervous system disorders | Systematic Assessment |
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| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |