Citicoline Treatment of Methamphetamine Dependence

胞磷胆碱治疗甲基苯丙胺依赖

基本信息

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
项目类别：
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

项目摘要

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) 依赖是一种高度致残且难治的疾病，会导致社交和职业功能严重受损。尽管MA的使用流行情况似乎已经稳定，但MA仍然是世界上第二大使用最广泛的非法药物，并且与MA使用相关的公共卫生问题继续增加。然而，迄今为止，美国 FDA 还没有批准用于治疗 MA 依赖的药物，临床上仍然需要更有效的药物疗法。因此，我们建议将胞二磷胆碱（CDP-胆碱作为营养补充剂）用于 MA 依赖的潜在辅助治疗，作为对 RFA-DA-09-005“物质相关疾病药物治疗试点临床试验”的回应。胞二磷胆碱已被证明可有效治疗多种中枢神经系统疾病。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。我们利用多模式神经影像学方法来研究 MA 依赖性。最近，我们发现胞二磷胆碱往往会减少 MA 的使用，更重要的是，会增加 MA 依赖受试者的额叶 N-乙酰天冬氨酸（NAA，神经元活力或完整性的标志物）水平，这表明神经元活力和认知功能的恢复。慢性 MA 受试者存在认知缺陷，包括执行功能、情景记忆和信息处理速度受损，以及语言记忆/流畅性和抑制功能受损。认知缺陷与 MA 使用复发和无效的心理社会治疗结果密切相关。胞二磷胆碱可能会减弱使用 MA 的欲望并改善认知表现，从而使有动机的受试者的治疗更加有效。拟议研究的目的是系统评估胞磷胆碱对 74 名 MA 依赖的年轻人的治疗效果。将进行为期八周的随机、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 名健康受试者也将被纳入与 MA 依赖受试者进行基线和随访比较。我们计划从评估和转介服务 (ARS) 接收参与者转介，该服务每年为数千名患有药物滥用障碍且没有健康保险的盐湖县居民提供评估。在此应用中，我们将利用神经心理学测量和多模态神经影像技术（例如磁共振波谱、扩散张量成像和脑皮质厚度测量）来研究胞二磷胆碱在减少药物使用和改善脑功能方面的功效。我们认为神经影像学是并行检查的重要工具，因为它提供了与治疗相关的体内大脑结构和功能变化的重要信息。公共卫生相关性：本申请将评估胞二磷胆碱作为等待治疗的 MA 依赖性受试者的辅助治疗作用。为期 8 周的胞二磷胆碱试验后，神经心理功能和多模式神经影像学的补充测量将为这一重大公共卫生问题提供新的见解和治疗策略。