Methadone Studies

美沙酮研究

• 批准号: 8470147
• 负责人: THOMAS Richard KOSTEN
• 金额: $ 25.39万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8470147
• 关键词: Adrenergic Antagonists; Adrenergic Receptor; Adverse effects; Alleles; Attenuated; Behavior; Biology; Clinical Trials; Cocaine; Cocaine Dependence; Code; Cognitive Therapy; Dependence; Disease; Disulfiram; Dopamine; Dopamine-beta-monooxygenase; Dose; Double-Blind Method; FDA approved; Genetic; Genetic Polymorphism; Genotype; Haplotypes; Heart failure; Hour; Human; Instruction; Knowledge; Laboratories; Lead; Literature; Measures; Medical; Methadone; Methamphetamine dependence; Methods; Norepinephrine; Norepinephrine Receptors; Nucleus Accumbens; Opioid; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Pharmacogenetics; Pharmacotherapy; Placebo Control; Placebos; Post-Traumatic Stress Disorders; Prazosin; Promoter Regions; Psychotherapy; Public Health; Randomized; Randomized Clinical Trials; Reaction; Receptor Gene; Reporting; Rewards; Role; Safety; Side; Testing; Therapeutic; Treatment Efficacy; Treatment outcome; United States; Urinalysis; Variant; Work; aged; alpha-1 adrenergic receptors; base; cocaine use; experience; improved; inhibitor/antagonist; nepicastat; neurotransmission; noradrenergic; primary outcome; promoter; prospective; response; screening; treatment response

PROJECT SUMMARY (See instructions): Comorbid cocaine dependence among methadone maintained patients interferes with treatment outcomes. Prazosin (alphai-adrenergic antagonist) and DpH inhibition (disulfiram) have shown promising results in the treatment of cocaine dependence. While inhibition of DpH activity is hypothesized to increase dopamine (DA) but decrease norepinephrine neurotransmission and to intensify the dysphoric experience of cocaine use, the selective inhibition of alphai-adrenergic receptor antagonist is hypothesized to attenuate DA neurotransmission primarily in the nucleus accumbens and to reduce the reinforcing effects of cocaine use. The objective of this proposal is to determine to what extend does prospective screening for a functional polymorphism of dopamine beta hydroxylase (DBH-1021C¿vT) or polymorphisms in the promoter region and the coding region ofthe alpha-la-adrenoceptor receptor gene (ADRAIA) predict the treatment efficacy of nepicastat (a new DpH inhibitor) or prazosin among newly admitted methadone treated patients. Based on our previous studies, we hypothesize that carriers ofthe low-OpH associated T allele will have significant reductions in cocaine use, because they are more susceptible to inhibition of DpH by nepicastat. We also will assess post-hoc the impact of functional variants ofthe ADRAIA on the response to prazosin. This 12- week double-blind, placebo controlled randomized clinical trial will provide treatment for 150 cocainedependent opioid dependent patients who have 2-weeks of methadone induction and 4 week discontinuation for 18-weeks total. Participants, aged 18-65 years, will be randomized to receive prazosin 10 mg/day, nepicastat 120mg/day, or placebo while concurrently receiving treatment with methadone. All participants receive weekly 1-hour psychotherapy (Cognitive Behavioral Treatment). The primary outcomes will be reduction in opioid and cocaine use, as assessed by self-report and confirmed by thrice-weekly urinalyses. The proposed study is expected to provide a better understanding ofthe role ofthe DpH inhibitor nepicastat and the selective alphaiA adrenergic receptor antagonist prazosin on cocaine using behavior among distinct DBH -1021C-+T genotypes or the functional variants in the promoter and coding region of ADRA1A.

项目摘要（请参阅说明）： MethodOne之间可卡因的合并可卡因依赖性维持患者会干扰治疗结果。 prazosin（Alphai-gen肾上腺素能拮抗剂）和DPH抑制（二硫兰氏蛋白酶）在治疗可卡因依赖性方面表现出了希望的结果。虽然假设抑制DPH活性以增加多巴胺（DA），但会降低去甲肾上腺素神经传递并增强可卡因的烦躁经历 假设使用，选择性抑制α-肾上腺素能受体拮抗剂可以减轻伏伏核中的DA神经传递的一级，并减少可卡因使用的增强作用。 该提案的目的是确定什么扩展是为多巴胺β羟基羟化酶（DBH-1021C¿VT）或启动子区域中的多态性的功能性多态性和多态性筛查的前瞻性筛查，并且在alpha-la-la-la-la-ra-ra-ra-ra-aprenrenoceptor受体基因（Adraia）之间的编码区域预测了NEPAST INEPAST INPERAST INPAST INPAST INPAST INPAST INPERAST（NEPESTICININ）。新入院的MEDADANE治疗患者。基于我们以前的研究，我们假设低磷相关的T等位基因的载体将大幅降低可卡因的使用，因为它们更容易受到Nepicastat抑制DPH的影响。我们还将在事后评估Adraia功能变异对prazosin的反应的影响。这个12- 周期双盲，安慰剂对照的随机临床试验将为150名依赖性阿片类药物依赖性患者提供治疗，这些患者患有2周的方法adone诱导和4周停止，总计18周。年龄在18-65岁的参与者将被随机分配以获得prazosin 10毫克/天， Nepicastat 120mg/天，或安慰剂，同时接受Metagadone进行治疗。所有参与者每周接受1小时的心理治疗（认知行为治疗）。正如自我报告评估的，主要结果将减少阿片类药物和可卡因的使用，并通过每周三次的尿液线路确认。 预计拟议的研究将更好地理解DPH抑制剂Nepicastat和选择性αIA肾上腺素受体拮抗剂普拉唑嗪在可卡因对可卡因的作用，其中使用不同的DBH -1021C-+T基因型或Adra1a启动子和编码器区域的功能变体中的行为中的行为。