SAMe for Smoking Abstinence

SAMe 戒烟

• 批准号: 7373119
• 负责人: AMIT SOOD
• 金额: $ 18.89万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7373119
• 关键词: Abstinence; Adult; Adverse effects; Behavioral; Blinded; Brain; Chronic; Cigarette Smoker; Clinic; Clinical Trials; Conduct Clinical Trials; Counseling; Data; Dopamine; Dose; Enrollment; Excess Mortality; Funding Mechanisms; Goals; Health Care Costs; Intake; Intervention; Mediating; Methionine; Minnesota; Morbidity - disease rate; Neuraxis; Neurotransmitters; Nicotine; Nicotine Withdrawal; Norepinephrine; Nucleus Accumbens; Oral; Oral cavity; Participant; Patients; Personal Satisfaction; Pharmaceutical Preparations; Phase II Clinical Trials; Phase III Clinical Trials; Placebo Control; Placebos; Prevalence; Public Health; Publishing; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Range; Rate; Recruitment Activity; Relapse; Research; Rewards; Risk; Smoke; Smoker; Smoking; Symptoms; System; Testing; Time; Tobacco; Tobacco Dependence; Tobacco use; United States; Upper arm; Week; Withdrawal; Withdrawal Symptom; cigarette smoking; craving; day; design; improved; innovation; methyl group; monoamine; novel; presynaptic; programs; prospective; smoking cessation; smoking prevalence; tobacco abstinence

DESCRIPTION (provided by applicant): Cigarette smoking is of great public health importance and is the single most important preventable cause of morbidity, mortality and excess health care costs in the United States. After a steady decline for the last 50 years, the prevalence of tobacco use in the United States has reached a plateau of approximately 21%. Currently available treatments among adults are not efficacious for all tobacco users. New pharmacologic agents thus need to be continually developed and tested. The release of dopamine in the nucleus accumbens is one of the key components of the pleasurable and rewarding effects of nicotine. Drugs that increase monoamine neurotransmitter availability (particularly dopamine and norepinephrine) are likely to increase the reward function and thus ameliorate withdrawal symptoms. S-Adenosyl-L-Methionine (SAMe), the primary methyl donor for the central nervous system (CNS), donates methyl groups towards presynaptic synthesis of CNS monoamine neurotransmitters. By facilitating the synthesis of dopamine and norepinephrine in the brain, SAMe is likely to ameliorate the symptoms of nicotine withdrawal, thus improving tobacco abstinence rates in smokers who are trying to stop smoking. SAMe is well tolerated and is available over-the-counter. To date, no prospective clinical trial evaluating the efficacy of SAMe for the treatment of tobacco dependence has been published. We propose to evaluate the efficacy of SAMe for increasing smoking abstinence and decreasing nicotine withdrawal symptoms in a randomized, blinded, placebo-controlled, three arm, parallel-group, dose-ranging phase II clinical trial. Participants (N=120) will be randomly assigned to one of the three groups, and will receive an 8-week course of SAMe 800-mg per day, 1600-mg per day, or a matching placebo. This study is anticipated to provide the data needed to develop a larger randomized controlled clinical trial submitted through the R01 funding mechanism, if the results appear promising.

描述（由申请人提供）：吸烟非常重要，是美国发病，死亡率和过剩医疗费用的最重要的唯一可预防原因。在过去50年中稳步下降之后，美国使用烟草的流行率约为21％。目前，成年人的可用治疗对所有烟草使用者都没有有效。因此，新的药理学剂需要不断开发和测试。多巴胺在伏隔核中的释放是尼古丁愉悦和有益作用的关键组成部分之一。增加单胺神经递质可用性（尤其是多巴胺和去甲肾上腺素）的药物可能会增加奖励功能，从而改善戒断症状。中枢神经系统（CNS）的主要甲基供体S-腺苷-L-甲硫氨酸（相同）将甲基捐赠给CNS单胺神经递质的突触前合成。通过促进大脑中多巴胺和去甲肾上腺素的合成，也可能可以缓解戒断尼古丁的症状，从而提高试图停止吸烟的吸烟者的烟草戒烟率。相同的耐受性且可在非处方线上可用。迄今为止，还没有发表前瞻性临床试验来评估烟草依赖性治疗的功效。我们建议评估在随机，盲，盲，安慰剂对照的，三个ARM，平行组，剂量增加剂量的II期临床试验中，在随机，盲，安慰剂对照中增加戒烟和减少尼古丁戒断症状的疗效。参与者（n = 120）将随机分配给三组之一，并将获得每天800毫克相同的800毫克，每天1600毫克或匹配的安慰剂的8周课程。如果结果似乎有希望，预计这项研究将提供通过R01资金机制提交的更大随机对照临床试验所需的数据。