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）：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，根据全国药物使用和药物调查，过去三年中有超过 200 万人开始滥用这些药物。健康。鉴于已知阿片类药物成瘾是慢性且复发的，并会导致个人和社会公共卫生问题（个人发病率和死亡率、传染病传播增加和犯罪），因此需要针对这种疾病的更有效的治疗方案。目前批准的治疗阿片类药物依赖的维持药物虽然有效，但由于患者接受度有限（纳曲酮）、可用性有限（美沙酮）以及对转移的担忧（美沙酮和丁丙诺啡）而受到阻碍。曲马多是一种具有阿片类激动剂活性的非典型镇痛药，不受《管制物质法》的控制，相对于其他完全 mu-阿片类激动剂，滥用可能性降低，可能是阿片类药物依赖的有效治疗方法。这项为期两周的随机、安慰剂对照住院研究分为两个阶段，每个阶段都有一个主要目标。第 1 阶段（第 1-7 天）将评估缓释 (ER) 曲马多治疗短效处方阿片类药物戒断的戒断抑制功效。第 2 阶段（第 8-14 天）将评估紧急停止 ER 曲马多给药后戒断的特征和严重程度，并将提供有关阿片类激动剂作用强度和曲马多产生的依赖性潜力的进一步信息。年龄在 18-55 岁之间，阿片类药物尿液样本呈阳性，自我报告过去 30 天内至少 21 天内使用短效阿片类药物，符合处方阿片类药物依赖（其他方面健康）的诊断标准的人士将符合资格用于住院研究单位的住院治疗。第一次过夜后（以确保一段时间的阿片类药物戒断），表现出明显阿片类药物戒断迹象的参与者将被随机接受三种双盲治疗中的一种：安慰剂或缓释曲马多（每天 400 或 800 毫克，分两次服用）匹配的胶囊）。分层将根据经过培训的工作人员在随机分组前立即评估的客观阿片类药物戒断严重程度（低、中和高）的三个级别进行。每个治疗组需要 12 名受试者来完成 (n=36)。曲马多剂量将在前 24 小时内逐步增加，以减少出现副作用的可能性。所有群体均可使用辅助药物来治疗突破性戒断。主要结局指标包括参与者评定的阿片类药物形容词戒断量表以及在研究的每个阶段用于突破性阿片类药物戒断的辅助药物量。将收集许多次要结果指标。本研究收集的数据将提供关于 ER 曲马多的剂量相关戒断抑制功效的新颖且重要的信息，并确定曲马多在急性停药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对处方阿片类药物依赖进行更大规模的评估。 公共卫生相关性：处方阿片类药物成瘾是一个日益严重的公共卫生问题，需要更多的药物治疗，因为目前批准的药物患者接受度有限（纳曲酮），可用性有限（美沙酮），并且担心滥用和转移（美沙酮和丁丙诺啡）。曲马多是目前批准用于治疗中度至重度疼痛的药物，初步研究表明，它可能有助于治疗阿片类药物戒断引起的不适综合征，且不会产生欣快感。这项研究将确定两种不同剂量的缓释曲马多是否可以治疗阿片类药物戒断，以及曲马多本身在不再服用后是否会产生戒断症状。