The Jefferson Regional Clinical Center for Heart Failure Network

心力衰竭（HF）的病理生理模型已从简单的血液动力学模型发展到 更复杂的模型，包括神经激素和细胞因子成分。促炎细胞因子， 其比神经激素更早表达，在细胞外基质周转中起关键作用， 包括基质金属蛋白酶（MMPs）的调节。目前，没有批准的药物 其直接靶向肿瘤坏死因子（TNF）-α或MMPs。TNF-a和MMP表达增加 与适应不良的心脏重塑相关，并已被确定为 HF患者的生存率。亚抗微生物多西环素（SDD）已被证明可减少肿瘤细胞中的TNF-α和MMP。 其他慢性疾病，但尚未在HF患者中进行评估，部分原因是其不再具有专利 保护和作为仿制药出售。亚抗菌药物强力霉素治疗对急性胰腺炎疗效的影响 心力衰竭患者的身体功能和舒张末期容积模式（STOPPED-HF）研究是一项 在200例HF队列中评价SDD效应的双盲、随机、前瞻性、II期临床试验 左心室功能降低的受试者。主要假设是SDD将显著降低 治疗12个月后HF患者左心室舒张末期容积指数的变化。此外，本发明还提供了一种方法， SDD将改善身体功能和生活质量;并降低MMP和肿瘤坏死因子α。 药物不良反应也将作为研究的一部分进行随访。STOPPED-HF研究是科学的， 杰斐逊地区临床中心（RCC）提出的申请参加 NHLBI心力衰竭临床研究网络。杰斐逊RCC汇集了3个最大的 特拉华州山谷的卫生保健系统：托马斯杰斐逊大学（公共关系学：大卫惠兰博士;公司 研究者Raphael Bonita博士）、坦普尔大学（共同研究者：Alfred Bove博士）和Christiana Care （共同研究者：Mitchell Saltzberg博士）。这些中心将提供参与高频网络协议， 大量HF患者人群，包括重要的少数民族和女性人群。认识到 包括LV功能保留的HF患者，申请包括参与部门 家庭医学（合作研究者; Geoffrey米尔斯博士）。杰斐逊RCC将利用其参与 HF网络，建立K30计划和世界著名的HF研究人员建立杰斐逊 临床研究技能开发核心（核心负责人：Walter Kraft博士;导师：亚瑟费尔德曼博士， 托马斯福斯、保罗马瑟和大卫惠兰）。 相关性（参见说明）： 加强心力衰竭患者的新疗法渠道对于降低高发病率和 这一患者群体继续遭受的死亡率。评估低成本治疗，如 在较小的2期临床试验中，多西环素的一般可用的亚抗菌剂量提供了 在组织更大规模的临床试验之前，向研究人员和资助机构提供必要的数据。

The pathophysiologic model for heart failure (HF) has advanced from a simple hemodynamic model to a more complicated model that includes neurohormonal and cytokine components. Proinflammatory cytokines, which are expressed eariier than neurohormones, play a critical role in extracellular matrix turnover, including the regulation of matrix metalloproteinases (MMPs). Currently, there are no approved medications that directly target tumor necrosis factor (TNF) -a or MMPs. Increased expression of TNF-a and MMP is associated with maladaptive cardiac remodeling and has been identified as an independent predictor of survival in HF patients. Sub-antimicrobial doxycycline (SDD) has been shown to reduce TNF-a and MMPs in other chronic diseases but has not been evaluated in HF patients due in part to it no longer having patent protection and being sold as a generic drug. The Sub-antimicrobial Doxycycline Therapy on Outcomes of Physical Function and Patterns of End-Diastolic Volume in Heart Failure Patients (STOPPED-HF) Study is a double blinded randomized prospective phase 2 clinical trial of the effects of SDD in a cohort of 200 HF subjects with reduced left ventricular function. The primary hypothesis is that SDD will significantly reduce left ventricular end diastolic volume index changes in HF patients over 12 months of treatment. In addition, SDD will improve physical function and quality of life; and reduce MMP and tumor necrosis factor alpha. Adverse drug reactions will also be followed as part of the study. The STOPPED-HF study is the scientific protocol proposed by the Jefferson Regional Clinical Center (RCC) for its application to participate in the NHLBI's Heart Failure Clinical Research Network. The Jefferson RCC brings together 3 of the largest healthcare systems in the Delaware Valley: Thomas Jefferson University (Pl: Dr. David Whellan; co investigator Dr. Raphael Bonita), Temple University (co-investigator: Dr. Alfred Bove) and Christiana Care (co-investigator: Dr. Mitchell Saltzberg). These centers will offer participation in HF Network protocols to a large HF patient population, including a significant minority and female population. Recognizing the goal of including HF patients with preserved LV function, the application includes participation of the Department of Family Medicine (co-investigator; Dr. Geoffrey Mills). The Jefferson RCC will leverage its participation in the HF Network, the established K30 program and worid-renowned HF researchers to establish the Jefferson Clinical Research Skills Development Core (Core Leader: Dr. Walter Kraft; mentors: Drs. Arthur Feldman, Thomas Force, Paul Mather and David Whellan). RELEVANCE (See instructions): Enhancing the pipeline of new therapies for heart failure patients is critical to reducing the high morbidity and mortality that this patient population continues to suffer. Evaluating low-cost treatments, such as the generically available sub-antimicrobial dosing of doxycycline, in smaller phase 2 clinical trials provides the necessary data to inform researchers and funding agencies prior to organizing larger clinical trials.