Neurocognitive Effects of Opiate Agonist Treatment
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 135
- 试验地点
- 2
- 主要终点
- Global Neurocognitive Function
研究概览
简要总结
The purpose of this study is to (1) compare the effects of buprenorphine and methadone, two types of opioid addiction treatment, on the ability to think and reason among people addicted to opiates, and who are either HIV negative or HIV positive; and (2) investigate whether HIV infection changes the way opioid treatment affects the ability to think and reason. The investigators hypothesize that there will be (1) significant improvement in thinking and reasoning ability after starting buprenorphine treatment compared to methadone treatment, among participants with and without HIV at 2 and 4 months compared to baseline; and (2) HIV positive participants will demonstrate significant improvement in thinking and reasoning ability at 2 and 4 months compared to baseline, but that their thinking and reasoning ability will still be lower than HIV negative participants.
详细描述
After randomization, each medication will be prescribed and administered by one of these experienced clinicians, according to well- established national protocols. Participants will be randomized in a 1:1 ratio in variable size blocks of 4-8 via central, computer-generated randomization. Given the relatively small sample size, we will randomize in blocks to ensure comparison groups of approximately equal size. Because medication type will not be blinded, we will vary block size to prevent anticipation of treatment arm assignment. We will also stratify randomization by HIV status to ensure equal numbers of HIV-infected persons in each arm.
INTERVENTION DOSE. Doses of buprenorphine and methadone will be adjusted within pre-specified ranges to ensure that comparisons between the two treatments are based on individually optimized doses.
Buprenorphine (we will use the buprenorphine/naloxone combination exclusively) will be administered at a dose of 8 to 32 mg per day, though we expect most subjects not to exceed 24 mg per day. These doses approximate methadone doses of 60 to 100 mg daily, which are in the upper range of doses generally used in clinical practice, but are well-known to be most efficacious and are also most prevalent in DoSA. Since study clinicians will be experienced substance abuse treatment providers, some flexibility will be allowed within these parameters. Both buprenorphine and methadone will be administered daily as oral medications.
The study will have two phases: induction/stabilization (weeks 1 - 3) and maintenance (weeks 4 - 24).
During dose induction/stabilization, subjects will attend daily visits (Sx/week) with a study clinician and receive gradually increasing doses of medication (see below). The first week of induction/stabilization will be considered a run-in period; at the conclusion of this week participants will complete enrollment in the trial and also complete their first NP research visit. The purpose of the run-in period is to ensure that we enroll persons who are able to comply with all trial requirements.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 68 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18 - 68
- •English or Spanish speaking
- •Documentation of HIV Status
- •Opioid-dependent without having received medication treatment for opioid dependence within the previous 90 days
- •Negative pregnancy test, for women
- •No "street" use of methadone or buprenorphine
- •Willing to participate in all study components
- •Able to provide informed consent
- •Education > 6 years
- •Not acutely intoxicated
排除标准
- •Serious or unstable medical disease: liver disease (AST or ALT ≥ 3x ULN, elevated PT/INR, albumin <3.0 g/dl or evidence of decompensated cirrhosis);
- •Severe cardiovascular disease (MI, PTCA, unstable angina, CABG, and/or serious arrhythmia in the previous 6 months);
- •COPD (requiring supplemental oxygen or hospitalization in past 6 months);
- •End stage renal disease or creatinine clearance <30 mL/min
- •Neurological disease: head injury with LOC>24 hour, previous penetrating skull wound, focal brain lesion, history of neurosurgery, seizure disorder (not ETOH-related), non-HIV CNS opportunistic infection
- •Psychiatric disorders (schizophrenia or bipolar)
- •Benzodiazepine or alcohol dependence
- •Chronic pain conditions requiring opioid analgesics
研究组 & 干预措施
Buprenorphine
Oral sublingual tablet, 8-32 mg per day, administered daily for duration of 4 months
干预措施: Buprenorphine (Drug)
Methadone
Oral sublingual tablet, 60-100 mg per day, administered daily for duration of 4 months
干预措施: Methadone (Drug)
结局指标
主要结局
Global Neurocognitive Function
时间窗: 2 and 4 months
Metrics: A Global Deficit Score (GDS) is computed by adding deficit ratings of the component test measures, and dividing by total number of measures. (Please see list of component test measures under the Domain-Specific Neurocognitive Function outcome).
Domain-Specific Neurocognitive Function (i.e. in the domains of executive functioning, learning, memory, attention/working memory, processing speed, motor, and verbal functioning).
时间窗: 2 and 4 months
Metrics: Domain Deficit Scores (DDS) are created for each of the 7 cognitive ability domains. Deficit Scores can be analyzed as dichotomous variables to classify individual subjects as impaired or normal, or continuously. Executive Functioning -- Wisconsin Card Sorting Task-64 Item Version; Trail Making Test (Part B) Learning -- Hopkins Verbal Learning Test-Revised (Total Recall); Brief Visuospatial Memory Test-Revised (Total Recall) Memory -- Hopkins Verbal Learning Test (Delayed Recall Trial); Brief Visuospatial Memory Test-Revised (Delayed Recall Trial) Attention/Working Memory -- WAIS-III Letter Number Sequencing; PASAT Total Correct Processing Speed -- WAIS-III Digit Symbol; WAIS-III Symbol Search; Trail Making Test (Part A) Motor -- Grooved Pegboard Time (dominant hand); Grooved Pegboard Time (non-dominant hand)\] Verbal Functioning -- Controlled Oral Word Association Test (F-A-S); Semantic (Animal) Fluency
次要结局
未报告次要终点
研究者
Julia H. Arnsten
Principal Investigator
Albert Einstein College of Medicine