Effect of TNF-alpha Antagonism in Metabolism Syndrome

TNF-α 拮抗剂在代谢综合征中的作用

• 批准号: 6832595
• 负责人: LAUREN E BERNSTEIN
• 金额: $ 2.32万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2005-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832595
• 关键词: atherosclerosis; cardiovascular agents; cardiovascular disorder chemotherapy; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular pharmacology; clinical research; clinical trials; computed axial tomography; coronary disorder; human subject; human therapy evaluation; inhibitor /antagonist; insulin sensitivity /resistance; interleukin 6; metabolic syndrome; patient oriented research; photon absorptiometry; postdoctoral investigator; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): The metabolic syndrome is associated with inflammatory cytokines, including TNF-alpha, IL-6 and CRP. The role of these inflammatory markers in the etiology of cardiovascular disease is unclear, although investigators have speculated that anti-inflammatory therapy may have a role in the prevention of cardiovascular disease in this population. The purpose of the study is to examine the role of TNF-alpha blockade on other inflammatory markers predictive of CAD and on adiponectin, a newly recognized adipokine that may be protective against atherosclerosis. Although little is known about adiponectin's regulation, in vitro data from both animals and humans, suggest that TNF-alpha may cause suppression of adiponectin, thus worsening insulin sensitivity and dampening adiponectin's anti-inflammatory and antiatherosclerotic effects. The study will be a randomized double blind placebo controlled trial in metabolic syndrome subjects using Etanercept, a TNF-alpha antagonist, to evaluate the effect of TNF-alpha blockade on inflammatory cytokines, adiponectin levels, and insulin resistance. Insulin resistance will be evaluated with an insulin modified IV glucose tolerance test. Inflammatory cytokines, adiponectin, and insulin resistance will be measured before, during and after Etancercept treatment.

描述（申请人提供）：代谢综合征与炎性细胞因子相关，包括TNF-α、IL-6和CRP。这些炎症标志物在心血管疾病病因学中的作用尚不清楚，尽管研究人员推测抗炎治疗可能在预防该人群心血管疾病方面发挥作用。该研究的目的是检查 TNF-α 阻断对预测 CAD 的其他炎症标志物和脂联素（一种新近认识的脂肪因子，可能具有预防动脉粥样硬化作用）的作用。尽管人们对脂联素的调节知之甚少，但来自动物和人类的体外数据表明，TNF-α可能会抑制脂联素，从而恶化胰岛素敏感性并抑制脂联素的抗炎和抗动脉粥样硬化作用。 该研究将是一项在代谢综合征受试者中进行的随机双盲安慰剂对照试验，使用 TNF-α 拮抗剂依那西普 (Etanercept)，评估 TNF-α 阻断对炎症细胞因子、脂联素水平和胰岛素抵抗的影响。胰岛素抵抗将通过胰岛素改良静脉葡萄糖耐量试验进行评估。将在 Etancercept 治疗之前、期间和之后测量炎症细胞因子、脂联素和胰岛素抵抗。