A trial to determine the effect of psoriasis treatment on cardiometabolic disease

确定银屑病治疗对心脏代谢疾病影响的试验

• 批准号: 8423323
• 负责人: JOEL M GELFAND
• 金额: $ 71.85万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-08 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8423323
• 关键词: 2-Fluoro-2-deoxyglucose; Address; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Atherosclerosis; Biological Markers; Blood; Blood Vessels; CD4 Positive T Lymphocytes; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chronic; Clinical; Critical Pathways; Data; Deoxyglucose; Development; Disease; Dyslipidemias; Epidemiologic Studies; Ethics; Event; Functional disorder; Future; Grant; Helper-Inducer T-Lymphocyte; High Density Lipoproteins; Human; Image; Imaging Techniques; Immune; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Insulin Resistance; Intervention; Joints; Knowledge; Lesion; Link; Lipoproteins; Liver; Measurement; Measures; Mediating; Medical; Metabolic; Metabolic Pathway; Metabolism; Modality; Modeling; Myocardial Infarction; Nature; Observational Study; Organ; Pathogenesis; Pathway interactions; Patients; Perception; Pharmaceutical Preparations; Phenotype; Phototherapy; Placebos; Play; Population; Positron-Emission Tomography; Process; Psoriasis; Research; Rheumatoid Arthritis; Risk; Risk Factors; Skin; Spleen; Stroke; T-Lymphocyte; Testing; Tumor Necrosis Factor-alpha; X-Ray Computed Tomography; adalimumab; arm; base; cardiovascular risk factor; clinically significant; cytokine; fluorodeoxyglucose positron emission tomography; immune activation; immunoregulation; improved; in vivo; in vivo Model; inhibitor/antagonist; innovation; lipid metabolism; macrophage; patient population; premature; randomized placebo controlled trial; randomized trial; reverse cholesterol transport; tumor necrosis factor-alpha inhibitor; ultraviolet; vascular inflammation

DESCRIPTION (provided by applicant): Psoriasis affects over 7 million people in the US (125 million people worldwide) and is the most common helper T-cell (Th)-1, Th-17 mediated inflammatory disease in humans. Epidemiological studies indicate that psoriasis is associated with an increased risk for major cardiovascular (CV) events and premature death due to CV disease independent of traditional risk factors. It is not know if successful treatment of psoriasis modulates CV risk. Furthermore, treatment of psoriasis and other inflammatory disease states with tumor necrosis factor alpha inhibitors (TNF-I s) has reached over 1 million people and there are observational studies demonstrating modulation of lipoproteins and CV risk with these drugs, however, a randomized trial of these endpoints is necessary to confirm these findings. Given that inflammation is an important pathogenic process in cardiometabolic disease, reduction of inflammation systemically by treating psoriasis provides a human, in vivo model to understand the link between modulation of chronic inflammation and CV disease in a population where treatment of the disease is elective providing an ethical placebo arm. The recent development of 18[F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) for measuring vascular inflammation provides a modality to test this hypothesis in vivo. Furthermore, FDG PET CT addresses a critical barrier to progress in the field as it allows for dynamic in vivo measurement of vascular inflammation in a manner which is highly sensitive, reproducible, modifiable over a short term following intervention, and predictive of clinically important CV events. We have assembled highly skilled, diverse collaborators who are leaders in psoriasis cardiovascular research, PET/CT vascular imaging, lipoprotein metabolism and cardiovascular translational focused on inflammatory patho-mechanisms of metabolic and atherosclerotic disease. This team provides a significant opportunity to address the interdisciplinary nature of the problem of studying the interrelationship of two common, but phenotypically distinct diseases. We therefore propose a randomized, placebo controlled trial to determine if treatment of psoriasis improves vascular inflammation measured by FDG PET CT and cardiometabolic disease measured by known CV biomarkers (including dyslipidemia, HDL function, metabolic, and inflammatory-based measures) using three treatment arms: systemic immunomodulation with TNF-I s; skin-directed therapy with ultraviolet B (UVB) phototherapy; and placebo. Through the studies proposed, we will improve scientific understanding of how treatment with TNF-I s and UVB phototherapy modulate vascular inflammation and cardiometabolic disease in vivo and ex vivo compared to placebo. These results will be a critical step in determining how treatment of psoriasis affects CV risk in this vulnerable patient population and will concurrently improve scientific knowledge of off target effects of the commonly used TNF-I s.

描述（由申请人提供）：牛皮癣在美国（全球范围内的1.25亿人）影响了700万人，是人类最常见的助手T细胞（TH）-1，TH-17介导的炎症性疾病。流行病学研究表明，牛皮癣与由于CV疾病而与传统危险因素无关的CV疾病引起的主要心血管（CV）事件的风险增加。不知道成功治疗牛皮癣是否会调节简历风险。此外，用肿瘤坏死因子α抑制剂（TNF-I）治疗牛皮癣和其他炎症性疾病状态已达到100万人的范围，并且有观察性研究表明，这些药物对这些端口的随机试验进行了调节，以确认这些发现的随机试验，以确认这些发现。鉴于炎症是心脏代谢疾病中重要的致病过程，因此通过治疗牛皮癣的炎症系统减少炎症为人类的体内模型提供了一个人的体内模型，以了解慢性炎症的调节与疾病治疗的人群中的调节之间的联系。最近使用正电子发射断层扫描（PET）/计算机断层扫描（CT）进行18 [F] -2-2-Fluoro-2-脱氧-D-葡萄糖（FDG）成像的发展，用于测量血管炎症，为在体内测试这一假设提供了一种方式。此外，FDG PET CT解决了该领域进展的关键障碍，因为它允许在干预后短期内高度敏感，可重复，可修改的方式进行体内测量血管炎症，并预测临床上重要的CV事件。我们组装了高技能，多样化的合作者，他们是牛皮癣心血管研究，PET/CT血管成像，脂蛋白代谢和心血管转化的领导者，专注于代谢性和动脉粥样硬化疾病的炎症性病理学。该团队提供了一个重要的机会，以解决研究两种常见但表型不同疾病的相互关系问题的问题的跨学科性质。因此，我们提出了一项随机的，安慰剂对照试验，以确定牛皮癣的治疗是否改善了通过已知CV生物标志物测量的FDG PET CT和心脏代谢疾病测量的血管炎症（包括使用三种治疗武器：系统性免疫机能与Tnf-i s;紫外线B（UVB）光疗的皮肤定向治疗；和安慰剂。通过提出的研究，我们将提高对TNF-I和UVB光疗治疗的科学理解，与安慰剂相比，体内和Ex Vivo的血管炎症和心脏代谢疾病调节。这些结果将是确定牛皮癣治疗如何影响该脆弱患者人群中简历风险的关键步骤，并同时改善常用TNF-I的关闭目标影响的科学知识。