Memantine-enhanced Buprenorphine Treatment for Opioid-dependent Young Adults

美金刚增强丁丙诺啡治疗阿片类药物依赖的年轻人

• 批准号: 8075095
• 负责人: Gerardo Gonzalez
• 金额: $ 39.54万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8075095
• 关键词: 21 year old; Abstinence; Adult; Adverse effects; Adverse event; Aftercare; Age; Agonist; Animals; Attenuated; Behavior; Buprenorphine; Chronic; Clinical; Clinical Trials; Cognitive; Combination Medication; Data; Development; Disease; Dose; Drops; Drug usage; Equilibrium; Glutamates; Group Therapy; Heroin; Human; Illicit Drugs; Impulsive Behavior; Individual; Intervention; Learning; Length; Locomotion; Maintenance; Maintenance Therapy; Measures; Memantine; Methadone; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Opiate Addiction; Opiates; Opioid; Oral; Participant; Patient Self-Report; Patients; Pattern; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Physical Dependence; Pilot Projects; Placebos; Population; Process; Public Health; Randomized; Randomized Clinical Trials; Relapse; Reporting; Research; Rewards; Risk; Role; Self Administration; Severities; Signal Transduction; Substance abuse problem; Time; Toxicology; Treatment outcome; Urine; addiction; aged; alternative treatment; base; clinical practice; common treatment; design; drug seeking behavior; effective therapy; gain of function; improved; indexing; innovation; mu opioid receptors; neurotransmission; opioid abuse; pre-clinical; preclinical study; prescription opioid; primary outcome; psychosocial; public health relevance; receptor function; secondary outcome; treatment duration; treatment program; young adult

DESCRIPTION (provided by applicant): Heroin use and non-medical use of prescription opioid continue to be a Public Health problem. Young adults are an especially important group because of the high rates of current use of illicit drugs (19.7 %). Opiate addiction is considered a chronic and relapsing disorder, and while agonist maintenance treatment continues to be the most common treatment for opiate dependence, the strong evidence of beneficial effects are mostly during the substitution period, but not during the post-treatment period when relapse and risk of returning to previous patterns of drug use are high. Growing preclinical evidence strongly suggests that the co-administration of an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist such as memantine with an opioid agonist may facilitate the sustainability of the opioid agonist efficacy on the mu-opioid receptor while at the same time and same animal reduce the sensitization to short-acting opiates' reinforcing effects. The purpose of this pilot clinical trial is to examine to what extent the co-administration of memantine (15mg & 30mg) to buprenorphine will improve treatment outcomes during and after treatment compared to buprenorphine alone. This 13-week clinical trial will provide treatment for 60 opioid dependent patients, aged 18-25 years, who will be randomized to three treatment conditions: (1) memantine 15mg/day + buprenorphine; (2) memantine 30mg/day + buprenorphine and (3) placebo + buprenorphine. The study will have an induction, maintenance and discontinuation phases. Baseline measures related to opioid use will be determined during the first week of treatment participation. Subjects' randomization will be balanced by severity of opioid dependence. All participants will participate in weekly group therapy. The primary outcomes will be weekly rates of self-reported use of opiates and urine toxicology during treatment with buprenorphine; rates of early relapse by self-report use of opiates and urine toxicology; and rates of side-effects and adverse events. The research proposed in this application is innovative because memantine enhanced time-limited buprenorphine therapy may become an effective alternative short-term intervention for many young adult patients. PUBLIC HEALTH RELEVANCE: Heroin use and non-medical use of prescription opioids among young adults continues to increase. Opiate addiction is considered a chronic and relapsing disorder that is effectively treated with long-term maintenance on agonist therapy. This treatment may not necessarily be the best treatment for young adults. This study is evaluating if adding memantine to buprenorphine may become an effective alternative short-term intervention for many young adult patients, and change current clinical practice for this population.

描述（由申请人提供）：海洛因使用和处方阿片类药物的非医疗使用仍然是一个公共卫生问题。年轻人是一个特别重要的群体，因为目前非法药物的使用率很高（19.7%）。阿片成瘾被认为是一种慢性和复发性疾病，虽然激动剂维持治疗仍然是阿片依赖最常见的治疗方法，但有益效果的有力证据主要是在替代期间，而不是在治疗后时期，因为此时复发和恢复到以前的吸毒模式的风险很高。越来越多的临床前证据强烈表明，非竞争性 N-甲基-D-天冬氨酸 (NMDA) 受体拮抗剂（例如美金刚）与阿片类激动剂的共同给药可能会促进阿片类激动剂对 mu-阿片受体功效的可持续性，同时在同一动物上降低对短效阿片类药物增强作用的敏感性。该试点临床试验的目的是检查与单独使用丁丙诺啡相比，美金刚（15 毫克和 30 毫克）与丁丙诺啡联合给药在治疗期间和治疗后能在多大程度上改善治疗结果。这项为期13周的临床试验将为60名年龄在18-25岁的阿片类药物依赖患者提供治疗，他们将被随机分配到三种治疗条件：（1）美金刚15mg/天+丁丙诺啡； (2) 美金刚 30 毫克/天 + 丁丙诺啡和 (3) 安慰剂 + 丁丙诺啡。该研究将分为诱导期、维持期和终止期。与阿片类药物使用相关的基线措施将在治疗参与的第一周内确定。受试者的随机化将根据阿片类药物依赖的严重程度进行平衡。所有参与者将参加每周的团体治疗。主要结果是丁丙诺啡治疗期间每周自我报告的阿片类药物使用率和尿液毒理学；根据阿片类药物使用情况和尿液毒理学的自我报告，早期复发率；以及副作用和不良事件的发生率。本申请中提出的研究具有创新性，因为美金刚增强限时丁丙诺啡疗法可能成为许多年轻成年患者的有效替代短期干预措施。 公共卫生相关性：年轻人中海洛因的使用和处方阿片类药物的非医疗使用持续增加。阿片成瘾被认为是一种慢性复发性疾病，通过长期维持激动剂治疗可以有效治疗。这种治疗可能不一定是年轻人的最佳治疗方法。这项研究正在评估在丁丙诺啡中添加美金刚是否可能成为许多年轻成年患者的有效替代短期干预措施，并改变该人群当前的临床实践。

项目成果

Buprenorphine-naloxone treatment responses differ between young adults with heroin and prescription opioid use disorders.

患有海洛因和处方阿片类药物使用障碍的年轻人对丁丙诺啡-纳洛酮的治疗反应有所不同。

• DOI: 10.1111/ajad.12641
• 发表时间: 2017
• 期刊: The American journal on addictions
• 作者: Romero-Gonzalez,Mauricio;Shahanaghi,Abtin;DiGirolamo,GregoryJ;Gonzalez,Gerardo
• 通讯作者: Gonzalez,Gerardo