Safety, Efficacy, and Mechanisms in American Ginseng in HIV-Related Fatigue

西洋参治疗 HIV 相关疲劳的安全性、功效和机制

• 批准号: 8333258
• 负责人: ADRIANA S.A. ANDRADE
• 金额: $ 59.73万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8333258
• 关键词: AIDS/HIV problem; Affect; American; Anti-Retroviral Agents; Botanicals; CYP2B6 gene; CYP3A4 gene; Cancer Patient; Chronic; Clinical Trials; Cytochrome P450; Data; Dose; Drug Formulations; Drug Interactions; Drug Kinetics; Enzymes; Etiology; Evaluation; Fatigue; Ginseng Preparation; Goals; HIV; HIV Infections; Hepatic; Herb; Herb-Drug Interactions; Inflammation; Integrase Inhibitors; Intervention; Isoenzymes; Knowledge; Lead; Marketing; Mediating; Metabolic Pathway; Metabolism; Morbidity - disease rate; Nucleosides; Oral Administration; Patients; Pharmaceutical Preparations; Physical Function; Placebo Control; Placebos; Plasma; Play; Protease Inhibitor; Protein Isoforms; Quality of life; Randomized; Reporting; Reverse Transcriptase Inhibitors; Role; Safety; Symptoms; Testing; Therapeutic; Toxic effect; Transferase; Treatment Failure; Zidovudine; abacavir; conventional therapy; coping; cytokine; drug efficacy; efavirenz; healthy volunteer; improved; in vivo; inhibitor/antagonist; non-nucleoside reverse transcriptase inhibitors; novel; psychologic; psychological distress

The goal of this proposal is to investigate the safety, efficacy, and mechanisms of action of American ginseng (AG) in the treatment of HIV-related fatigue, a widespread symptom in patients with HIV/AIDS that is associated with functional and psychological morbidity and poor quality of life. The mechanisms of HIV-related fatigue are not well understood; however, a role for increased concentrations of proinflammatory cytokines has been proposed. Few pharmacologic interventions are available to decrease fatigue in HIV-infected patients, and clinical trials of most have been limited. Peliminary data in cancer patients suggest that AG can improve fatigue. Thus, AG could also have therapeutic benefits for patients coping with HIV-related fatigue. AG is already widely used by patients with HIV/AIDS, alone or in combination with antiretroviral (ARV) drugs. However, despite its widespread use, the safety and efficacy of AG in treating HIV- related fatigue have not been formally evaluated. In particular, the herb-drug interactions between AG and ARV drugs have not been fully investigated. Herb-ARV interactions primarily involve the modulation of ARV-metabolizing cytochrome P450 (CYP450) isoenzymes, which in turn can alter drug efficacy and/or toxicity. Preliminary data indicate that AG does not significantly affect CYP3A4 activity, the major metabolic pathway for most ARV drugs. However, data are lacking for CYP2B6, another important isoenzyme. The following specific aims will test the hypothesis that a standardized AG formulation can improve HIV-related fatigue without causing significant herb-drug interactions: Aim 1. To determine the steady-state plasma concentrations of the CYP2B6 substrate efavirenz in healthy volunteers, before and after 14 days of concurrent treatment with AG. Aim 2. To determine the impact of AG on fatigue in HIV-infected patients in a randomized, placebo-controlled, dose-escalating (1000, 2000, and 3000 mg/day) clinical trial over 6 weeks. Proinflammatory cytokines will also be quantified in order to elucidate the mechanism of HIV-related fatigue and the effects of AG on these markers. This proposal will allow us to rigorously investigate a novel treatment for HIV- related fatigue and expand the current knowledge of herbal-ARV interactions.

本提案的目标是研究安全性、有效性和作用机制 西洋参（AG）在治疗艾滋病毒相关的疲劳，一个广泛的 艾滋病病毒/艾滋病患者的症状与功能和心理 发病率和生活质量差。HIV相关疲劳的机制尚不清楚 然而，促炎细胞因子浓度增加的作用 已经被提议了。很少有药物干预可以减少疲劳 在艾滋病毒感染者中，大多数的临床试验都很有限。初始数据 癌症患者建议AG可以改善疲劳。因此，AG也可以具有 治疗艾滋病相关疲劳的患者的好处。AG已经广泛 艾滋病病毒/艾滋病患者单独使用或与抗逆转录病毒（ARV）药物联合使用。 然而，尽管其广泛使用，AG在治疗HIV-1方面的安全性和有效性仍有待进一步研究。 相关疲劳尚未正式评估。特别是草药与药物的相互作用 AG和ARV药物之间的关系尚未得到充分研究。中草药-抗逆转录病毒相互作用 主要涉及ARV代谢细胞色素P450（CYP 450）的调节 同工酶，这反过来又可以改变药物功效和/或毒性。初步数据 表明AG不显著影响CYP 3A 4活性，CYP 3A 4是主要代谢酶， 大多数抗逆转录病毒药物的途径。然而，缺乏另一个重要的CYP 2B 6的数据， 同工酶以下具体目标将检验标准化AG 配方可以改善艾滋病毒相关的疲劳，而不会引起显着的草药 互动：目标1。测定CYP 2B 6的稳态血药浓度 健康志愿者中的底物依法韦仑，在14天并行治疗之前和之后 治疗AG。目标2.确定AG对HIV感染者疲劳的影响 随机、安慰剂对照、剂量递增（1000、2000和3000）的患者 mg/天）的临床试验。促炎细胞因子也将在 目的：探讨HIV相关性疲劳的发生机制及AG对其的影响。 标记。这项提议将使我们能够严格研究一种新的艾滋病毒治疗方法- 相关的疲劳和扩大目前的知识草药抗逆转录病毒相互作用。

项目成果

American ginseng (Panax quinquefolius) administration does not affect performance of the Roche COBAS Ampliprep/Taqman HIV-1 RNA assay.

服用西洋参 (Panax quinquefolius) 不会影响 Roche COBAS Ampliprep/Taqman HIV-1 RNA 检测的性能。

• DOI: 10.1186/1472-6882-14-427
• 发表时间: 2014
• 期刊: BMC complementary and alternative medicine
• 作者: Bakshi,RahulP;Brown,ToddT;Simmons,Antoine;Yuan,Chun-Su;Bauer,BrentA;Sloan,JeffA;Andrade,Adriana
• 通讯作者: Andrade,Adriana