Efficacy of Extended Release Tramadol for Treating Prescription Opioid Withdrawal

缓释曲马多治疗处方阿片类药物戒断的疗效

• 批准号: 7907591
• 负责人: Michelle Renee Lofwall
• 金额: $ 36.75万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7907591
• 关键词: 12 year old; Abstinence; Acute; Admission activity; Adverse effects; Age; Agonist; Analgesics; Buprenorphine; Cessation of life; Characteristics; Chronic; Cognition; Cognitive; Communicable Diseases; Crime; Data; Dependence; Diabetes Mellitus; Diagnostic; Disease; Dose; Double-Blind Method; Drug usage; Enrollment; Ensure; Evaluation; FDA approved; Health; Hepatic; Heroin; Hour; Hypertension; Illicit Drugs; Individual; Inpatients; Intravenous; Kentucky; Licensing; Life; Mainstreaming; Maintenance; Measures; Medical; Methadone; Moods; Morbidity - disease rate; Morphine; Naltrexone; Opiate Addiction; Opioid; Oral; Outcome Measure; Pain; Parents; Participant; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Phase; Physical Dependence; Pilot Projects; Placebo Control; Placebos; Population; Provider; Public Health; Questionnaires; Randomized; Randomized Controlled Trials; Relapse; Relative (related person); Reporting; Research; Route; Safety; Schedule; Screening procedure; Severities; Societies; Specimen; Stratification; Substance Withdrawal Syndrome; Surveys; Syndrome; Task Performances; Time; Training; Tramadol; United States; Universities; Urine; Variant; Withdrawal; addiction; arm; base; capsule; design; disease transmission; drug craving; effective therapy; epidemiologic data; meetings; monoamine; mortality; novel; opioid withdrawal; prescription opioid; prescription opioid abuse; primary outcome; public health relevance; reuptake; secondary outcome; volunteer

DESCRIPTION (provided by applicant): Approximately 1.7 million people in the United States met diagnostic criteria for prescription opioid abuse or dependence in 2007 and more than 2 million people initiated misuse of these medications in the last three years of the National Survey of Drug Use and Health. Given that opioid addiction is known to be chronic and relapsing and cause individual and societal public health problems (individual morbidity and mortality, increased transmission of infectious diseases, and crime), more efficacious treatment options for this disorder are needed. Currently approved maintenance medications for opioid dependence, while efficacious, have been hampered by limited patient acceptance (naltrexone), limited availability (methadone), and concerns about diversion (methadone and buprenorphine). Tramadol, an atypical analgesic with opioid agonist activity that is uncontrolled by the Controlled Substances Act, has reduced abuse potential relative to other full mu- opioid agonists and may be an effective treatment for opioid dependence. This two-week randomized, placebo-controlled inpatient study has two phases, each with one primary aim. Phase 1 (Days 1-7) will evaluate the withdrawal suppression efficacy of extended release (ER) tramadol for treatment of short-acting prescription opioid withdrawal. Phase 2 (Days 8-14) will assess the characteristics and severity of withdrawal from acute cessation of ER tramadol dosing and will provide further information about the strength of opioid agonist effects and dependence potential produced by tramadol. Persons age 18-55 years old with a positive observed opioid urine specimen, self-report of use of a short-acting opioid at least 21 out of the last 30 days, meeting diagnostic criteria for prescription opioid dependence (otherwise healthy) will be eligible for inpatient admission to the residential research unit. After the first overnight stay (to ensure a period of opioid abstinence), participants showing observable signs of opioid withdrawal will be randomized to one of three double-blind treatments: placebo or ER tramadol (400 or 800 mg daily given as two divided doses of matched capsules). Stratification will occur based on three levels of objective opioid withdrawal severity (low, medium, and high) as assessed by trained staff immediately prior to randomization. Twelve subjects will be needed to complete each treatment arm (n=36). Tramadol doses will be escalated over the first 24 hours to decrease chance of side effects. Ancillary medications are available to all groups to treat breakthrough withdrawal. Primary outcome measures include the participant-rated Opioid Adjectives Questionnaire Withdrawal Scale and amount of ancillary medication used for breakthrough opioid withdrawal during each Phase of the study. Numerous secondary outcome measures will be collected. The data gathered from this study will provide novel and important information regarding the dose-related withdrawal suppression efficacy of ER tramadol and determine whether tramadol produces a withdrawal syndrome after acute cessation. These results will be used to determine if a larger-scale evaluation of tramadol for prescription opioid dependence is warranted. PUBLIC HEALTH RELEVANCE: Prescription opioid addiction is a growing public health problem and more pharmacologic treatments are needed because current approved medications have had limited patient acceptance (naltrexone), limited availability (methadone), and concerns about misuse and diversion (methadone and buprenorphine). Tramadol is a currently approved medication used to treat moderate-severe pain, and initial studies demonstrate that it may be useful for treatment of the uncomfortable syndrome of opioid withdrawal without producing euphoric effects. This study will determine whether two different doses of extended release tramadol can treat opioid withdrawal and whether tramadol itself produces withdrawal after it is no longer taken.

描述（由申请人提供）：在2007年，美国大约有170万人符合处方阿片类药物滥用或依赖的诊断标准，并在全国对药物使用和健康调查的最后三年中遭受了滥用这些药物的滥用。鉴于已知阿片类药物成瘾是慢性和复发的，并引起个人和社会公共卫生问题（个人发病率和死亡率，传染病的传播增加以及犯罪），因此需要对这种疾病的更有效的治疗选择。目前，批准的阿片类药物依赖性维护药物有效地受到有限的患者接受（Naltrexone），有限的可用性（美沙酮）和对转移（美沙酮和丁丙诺啡）的担忧而受到阻碍的。 Tramadol是一种非典型镇痛药，具有阿片类药物的活性，受控物质法无法控制，相对于其他完全混合毒素激动剂，滥用潜力降低了潜力，并且可能是阿片类药物依赖性的有效治疗方法。这项为期两周的随机安慰剂对照的住院研究有两个阶段，每个阶段都有一个主要目标。第1阶段（第1-7天）将评估延长释放（ER）曲马多的戒断抑制功效，以治疗短期处方阿片类药物戒断。第2阶段（第8-14天）将评估因ER Tramadol剂量急性停止戒断的特征和严重程度，并将提供有关曲马多产生的阿片类药物激动剂作用和依赖潜力强度的进一步信息。 18-55岁的人患有阳性的阿片类尿液标本，使用短期作用阿片类药物的自我报告至少在过去30天中至少21天，符合处方阿片类药物依赖的诊断标准（其他健康）将有资格接受住院医师的住院医师入学。在第一次过夜过夜（为了确保阿片类药物的禁欲时期）之后，表现出可观察到的阿片类药物戒断迹象的参与者将被随机分为三种双盲治疗方法之一：安慰剂或ER Tramadol（每天400或800毫克，以两种分剂剂量的匹配胶囊））。分层将基于三个级别的客观阿片类药物戒断严重程度（低，中和高），如训练有素的工作人员在随机分组之前所评估。需要十二名受试者来完成每个治疗组（n = 36）。曲马多剂量将在最初的24小时内升级，以减少副作用的机会。所有小组都可以使用辅助药物来治疗突破性戒断。主要结果指标包括参与者评价的阿片类药物形容词问卷提取量表和在研究的每个阶段中用于突破阿片类药物戒断的辅助药物的量。将收集许多次要结果措施。从这项研究中收集的数据将提供有关ER Tramadol与剂量相关的戒断抑制功效的新颖和重要信息，并确定曲马多在急性停止后是否会产生戒断综合征。这些结果将用于确定是否有必要对曲马多进行大规模评估。 公共卫生相关性：处方阿片类药物成瘾是一个日益增长的公共卫生问题，需要更多的药理学治疗，因为当前批准的药物的患者接受程度有限（Naltrexone），有限的可用性（美沙酮）以及对滥用和转移的担忧（美沙酮和buprenorphine）。 Tramadol是一种目前批准的药物，用于治疗中度疼痛，最初的研究表明，它可能对治疗阿片类药物戒断的不舒服综合征有用，而无需产生欣快的作用。这项研究将确定两种不同剂量的扩展释放曲马多可以治疗阿片类药物的戒断，以及曲马多不再服用后是否会产生戒断。