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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：
9982831
负责人：
PERRY FRANKLIN RENSHAW
金额：
$ 48.9万
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/9982831
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 Drug Screening 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 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 conditioned place preference 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 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.

项目总结