A Randomized Double-Blind Controlled Trial of Creatine in Female Methamphetamine Users

女性甲基苯丙胺使用者肌酸的随机双盲对照试验

基本信息

批准号：
9250944
负责人：
PERRY FRANKLIN RENSHAW
金额：
$ 48.58万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9250944
关键词：
Abstinence Adenosine Triphosphate Adult Age Animals Anti-Anxiety Agents Antidepressive Agents Anxiety Apoptosis Base of the Brain Bioenergetics Biological Markers Brain Brain Chemistry Brain region Categories Chemicals Clinical Clinical Trials Clinical assessments Cognitive Cognitive Therapy Cognitive deficits Color Creatine Creatine Kinase Data Diet Disease Double-Blind Method Economic Burden Energy Metabolism Energy Supply Enrollment Equipment and supply inventories FDA approved Female Fishes GABA Receptor Gender Genes Glutamates Glutamine Goals Hamilton Rating Scale for Depression Health Impaired cognition Individual Intake Intervention Literature Magnetic Resonance Spectroscopy Maintenance Malnutrition Measures Meat Memory Mental Depression Methamphetamine Methamphetamine dependence Mitochondria Moods N-acetylaspartate Neurobehavioral Manifestations Neurons Neuropsychological Tests Neurotransmitters Nutritional Outcome Measure Pharmaceutical Preparations Pharmacotherapy Phosphocreatine Phosphorus Placebos Preclinical Drug Evaluation Prevention Protons Psychomotor Performance Psychostimulant dependence Randomized Rattus Reaction Recommendation Relapse Reporting Research Rodent Role Secondary to Selective Serotonin Reuptake Inhibitor Self Administration Site Sorting - Cell Movement Supplementation Symptoms System Test Result Testing Time Toxic effect Treatment Efficacy Urine Wisconsin Withdrawal Woman addiction anxiety symptoms base child depression cognitive enhancement cognitive function cognitive performance cognitive testing comorbid depression control trial craving depressive symptoms drug testing early onset executive function frontal lobe gamma-Aminobutyric Acid improved insight interest male men methamphetamine abuse methamphetamine use methamphetamine user mitochondrial dysfunction negative emotional state negative mood neurochemistry neuroimaging neurotoxicity novel novel therapeutics open label preference programs randomized placebo controlled trial relapse risk repaired restoration sex sustained attention volunteer

项目摘要

PROJECT SUMMARY Methamphetamine (MA) causes devastating harm to individuals, yet there are no approved treatments for MA use disorders. Female MA users have increased rates of depression, and more severe depressive symptoms than males. Depression may contribute to the risk of relapse because negative mood is associated MA craving. Our previous neuroimaging study found that female MA users have decreased frontal lobe phosphocreatine (PCr) levels, compared with both male MA users and female healthy controls. Following up on this key translational finding, preliminary data collected at our site suggests that when administered to female MA users, creatine monohydrate supplementation is associated with increased brain PCr, N-acetyl aspartate (NAA, a marker for neuronal health) and gamma-aminobutyric acid (GABA, the major inhibitory neurotransmitter of the brain). PCr is the substrate reservoir for the creatine kinase reaction, which reversibly converts PCr into adenosine triphosphate (ATP), the brain's major energy supply, and creatine. Clinically, creatine administration was associated with decreased depression and anxiety symptoms. It may also reduce MA use, measured by urine drug screens. This proposal follows expert recommendations to target cognitive enhancement, and neuronal repair, in developing pharmacotherapies for stimulant addiction. The long-term goal of this research program is to define the alterations in brain chemistry that underlie MA use disorders, and to utilize translational MRS neuroimaging to identify rational brain-based treatment targets. Once a hypothesis- driven intervention is identified, MRS can then be further employed in treatment studies, to verify that "target engagement" is achieved. In women with MA use disorders, creatine is a hypothesis-generated intervention aimed at restoring neurochemistry, reducing depression and anxiety symptoms, and improving cognitive function. Over a 5-year period, the project will enroll 76 women between the ages of 18 and 55 with MA use disorders and randomize them to 8 weeks of treatment with either creatine or placebo. Neuroimaging and cognitive testing of MA users will be performed at baseline, and repeated after 8 weeks of treatment. As outcome measures, multi-level assessments will be performed for brain chemistry, cognitive function, and clinical symptoms. It will be determined in female MA users whether creatine supplementation, compared to placebo, will 1) repair MA- induced neurochemical toxicity in the frontal brain regions, which will be assessed using phosphorus-31 and proton-1 multinuclear magnetic resonance spectroscopy (MRS), 2) improve depression and anxiety, which will be assessed using Hamilton Depression Rating Scale and Beck Anxiety Inventory tests, and 3) restore cognitive deficits associated with MA toxicity, which will be assessed using Wisconsin Card Sorting Task, the Stroop Color-Word Test, and the Wechsler Memory Scale. Additionally, urine drug testing results will be explored to determine the likelihood of reduced MA use following creatine supplementation.

项目摘要甲基苯丙胺（MA）对个人造成毁灭性伤害，但没有批准的治疗方法 MA使用疾病。女性MA使用者的抑郁率增加，更严重的抑郁症症状比男性。抑郁症可能导致复发的风险，因为负面情绪与众不同妈妈渴望。我们以前的神经影像学研究发现，女性MA使用者已减少额叶与男性MA使用者和女性健康对照组相比，磷酸盐（PCR）水平（PCR）水平。跟进在这一关键的翻译发现中，在我们网站收集的初步数据表明，当管理到女性MA使用者，补充肌酸一水合物与脑PCR增加有关天冬氨酸（NAA，神经元健康的标记）和γ-氨基丁酸（GABA，主要抑制作用大脑的神经递质）。 PCR是肌酸激酶反应的底物储层，可逆地将PCR转换为三磷酸腺苷（ATP），大脑的主要能量供应和肌酸。临床上肌酸给药与抑郁症和焦虑症状减轻有关。它也可能减少 MA使用，通过尿液药物筛查测量。该建议遵循专家建议以针对认知的建议在开发刺激性成瘾的药物疗法中，增强和神经元修复。长期该研究计划的目标是定义脑化学障碍和使用障碍的大脑化学变化，利用翻译MRS神经成像来识别基于大脑的理性治疗靶标。曾经是假设确定了驱动的干预措施，然后可以进一步用于治疗研究中，以验证“目标订婚”是实现的。在患有MA使用障碍的女性中，肌酸是一种假设生成的干预措施，旨在恢复神经化学，减轻抑郁和焦虑症状以及改善认知功能。超过5年期间，该项目将招募76名18至55岁的女性使用MA使用障碍并随机分组他们可以用肌酸或安慰剂进行8周的治疗。 MA用户的神经影像学和认知测试将在基线时进行，并在治疗8周后重复进行。作为结果措施，多层次将对脑化学，认知功能和临床症状进行评估。这将是在女性MA使用者中确定肌酸补充剂是否与安慰剂相比是否会）1）修复MA- 额叶区域的诱导神经化学毒性，将使用磷-31和质子-1多核磁共振光谱（MRS），2）改善抑郁和焦虑，这将使用汉密尔顿抑郁级评级量表和贝克焦虑量表测试以及3）还原评估与MA毒性相关的认知缺陷，将使用威斯康星州的卡分类任务评估， Stroop颜色词测试和Wechsler记忆量表。此外，尿液药物测试结果将是探索以确定补充肌酸后MA使用降低的可能性。