Citicoline Treatment of Methamphetamine Dependence

胞磷胆碱治疗甲基苯丙胺依赖

• 批准号: 7714896
• 负责人: PERRY FRANKLIN RENSHAW
• 金额: $ 37.63万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7714896
• 关键词: Abstinence; Accident and Emergency department; Admission activity; Adrenergic Agonists; Adverse effects; Age; Alcohols; Amphetamines; Anabolism; Anisotropy; Anterior; Anxiety; Attention; Attenuated; Behavior Therapy; Biological Factors; Brain; Bupropion; Caffeine; Cardiovascular system; Central Nervous System Diseases; Cerebrovascular Circulation; Cerebrum; Charge; Chemicals; Chronic; Client; Clinical; Clinical Treatment; Clinical Trials; Clinical Trials Design; Cocaine; Cocaine Dependence; Cocaine Users; Cognitive; Cognitive deficits; County; Cytidine Diphosphate Choline; Dependence; Diffusion Magnetic Resonance Imaging; Disease; Dopamine; Double-Blind Method; Dropout; Drops; Drug usage; Enrollment; Episodic memory; Evaluation; Exhibits; FDA approved; Generic Drugs; Goals; Gray unit of radiation dose; HIV; Health; Health Insurance; Hepatitis; Hospital Costs; Idaho; Illicit Drugs; Impairment; Individual; Insurance; Investigation; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Marijuana; Measurement; Measures; Medical; Membrane; Memory; Memory impairment; Meta-Analysis; Metabolism; Methamphetamine; Modafinil; Moods; Motor; N-acetylaspartate; Naltrexone; Names; Narcolepsy; Neuraxis; Neurons; Nicotine; Norepinephrine; Occupational; Oral; Outcome; Participant; Pathway interactions; Patient Self-Report; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phospholipids; Pilot Projects; Placebo Control; Placebos; Psychotic Disorders; Public Health; Randomized; Recovery; Refractory; Relapse; Relative (related person); Reporting; Request for Applications; Risk; Safety; Sampling; Services; Severities; Sodium Chloride; Sorting - Cell Movement; Structure; Substance abuse problem; Substance-Related Disorders; Symptoms; Techniques; Testing; Therapeutic Effect; Thick; Treatment outcome; Tyrosine; United States; Urine; Utah; Visual; Waiting Lists; Wisconsin; Withdrawal; Word Association Tests; base; blood flow measurement; cingulate cortex; cocaine use; cognitive change; cognitive function; craving; density; diaries; dietary supplements; drug craving; endogenous opioids; executive function; fluorodeoxyglucose positron emission tomography; follow-up; frontal lobe; glucose metabolism; gray matter; improved; in vivo; information processing; insight; methamphetamine abuse; morphometry; neuroimaging; neuropsychological; performance tests; processing speed; programs; prospective; psychosocial; psychostimulant; public health relevance; response; sex; single photon emission computed tomography; social; substance abuser; tool; transmission process; treatment program; treatment strategy; white matter; young adult

DESCRIPTION (provided by applicant): Methamphetamine (MA) dependence is a highly disabling and refractory condition, which results in serious impairment in social and occupational functioning. Although the endemic of MA use appears to have stabilized, MA is still the second most widely used illicit drug in the world, and the public health problem associated with MA use continues to increase. However, no medication to date has been approved by the FDA for the treatment of MA dependence in the United States and the clinical need for more effective pharmacotherapies remains significant. We therefore propose citicoline (CDP-choline as a nutritional supplement) for the potential adjunctive treatment of MA dependence as a response to RFA-DA-09-005, "Pilot Clinical Trials of Pharmacotherapies for Substance Related Disorders". Citicoline has demonstrated efficacy in treating a number of central nervous system disorders. The mechanism includes activation of the biosynthesis of structural phospholipids in neuronal membranes and an increase of norepinephrine and dopamine levels in the central nervous system. We have utilized a multi-modal neuroimaging approach for the investigation of MA dependence. Most recently, we have found that citicoline tends to decrease MA use and, importantly, to increase frontal lobe N-acetylaspartate (NAA, a marker of neuronal viability or integrity) levels in MA dependent subjects, which suggests recovery of neuronal viability and cognitive function. Chronic MA subjects have cognitive deficits, including impaired executive function, episodic memory and information processing speed, and verbal memory/fluency and inhibitory function. The cognitive deficits are closely related to both relapse to MA use and ineffective psychosocial treatment outcomes. Citicoline may attenuate desire for MA use and improve cognitive performance, making treatment more effective in motivated subjects. The goal of the proposed study is to systematically evaluate the therapeutic effects of citicoline in 74 MA dependent young adults. An eight week, randomized, prospective, double-blind, placebo-controlled, parallel group design, clinical trial will be conducted. Age, sex matched 37 healthy subjects also will be enrolled for baseline and follow-up comparison to MA dependent subjects. We plan to receive participant referrals from Assessment and Referral Services (ARS), which provides assessments for several thousand Salt Lake County residents with substance abuse disorders and no health insurance each year. In this application, we will take advantage of both neuropsychological measures and multimodal neuroimaging techniques such as magnetic resonance spectroscopy, diffusion tensor imaging and brain cortical thickness measure to investigate the efficacy of citicoline in reducing drug use and improving brain function. We believe neuroimaging is an essential tool for the parallel examination since it provides important information on treatment-related change in cerebral structure and function in vivo. PUBLIC HEALTH RELEVANCE: This application will evaluate citicoline as an adjunctive treatment in MA dependent subjects who are awaiting treatment. The complementary measures of both neuropsychological function and multimodal neuroimaging following an 8-week citicoline trial will provide new insights and treatment strategies for this significant public health concern.

描述（由申请人提供）：甲基苯丙胺（MA）依赖性是一种高度残疾和难治性的条件，这会导致社会和职业功能严重损害。尽管MA使用的地方性似乎已经稳定，但MA仍然是世界上第二大广泛使用的非法药物，与MA使用相关的公共卫生问题仍在增加。但是，FDA尚未批准迄今为止在美国治疗MA依赖性的药物，并且对更有效的药物治疗的临床需求仍然很大。因此，我们建议对MA依赖性的潜在辅助治疗作为对RFA-DA-09-005的反应，“ CDP-胆碱作为营养补充剂），“药物治疗相关疾病的药物治疗的临床试验”。 citicoline在治疗许多中枢神经系统疾病方面已显示出功效。该机制包括激活神经元膜中结构磷脂的生物合成，以及中枢神经系统中去甲肾上腺素和多巴胺水平的增加。我们利用一种多模式神经影像学方法来研究MA依赖性。最近，我们发现citicoline倾向于降低MA的使用，重要的是，在MA依赖性受试者中增加额叶N-乙酰天冬氨酸（NAA，神经元生存能力或完整性的标志），这表明神经元的生存能力和认知功能的恢复。慢性MA受试者具有认知缺陷，包括执行功能受损，情节记忆和信息处理速度以及口头记忆/流利性和抑制功能。认知缺陷与MA使用和无效的社会心理治疗结果密切相关。 citicoline可能会减弱对MA使用的渴望并改善认知表现，从而使治疗在动机受试者中更有效。拟议的研究的目的是系统地评估citicoline在74名MA依赖年轻人中的治疗作用。将进行八周的随机，前瞻性，双盲，安慰剂对照，平行组设计，临床试验。年龄，性别匹配的37名健康受试者也将参加基线和与MA依赖受试者的随访比较。我们计划从评估和推荐服务（ARS）中获得参与者的转诊，该转诊为数千名盐湖县居民提供滥用药物滥用障碍的评估，并且每年没有健康保险。在此应用中，我们将利用神经心理学措施和多模式神经影像学技术，例如磁共振光谱，扩散张量成像和脑皮质厚度措施，以研究citiceline在降低药物使用和改善脑功能方面的疗效。我们认为神经影像学是平行检查的重要工具，因为它提供了有关体内与治疗相关的脑结构变化和功能的重要信息。 公共卫生相关性：该应用将评估citicoline作为正在等待治疗的受试者的辅助治疗方法。为期8周的Citicoline试验后，神经心理学功能和多模式神经影像学的互补措施将为这一重大公共卫生关注提供新的见解和治疗策略。