Immune and Inflammatory Consequences of Intensive Periodontal Disease Treatment i

牙周病强化治疗的免疫和炎症后果 i

基本信息

批准号：
8111969
负责人：
LANCE T. VERNON
金额：
$ 19.43万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-15 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8111969
关键词：
Adult Advocate Age Animal Model Antibodies Atherosclerosis Awareness Bacteremia Bacteria Bacterial Infections Binding Biological Markers Blood Blood Vessels C-reactive protein CD14 gene CD4 Lymphocyte Count CD8B1 gene Campylobacter rectus Cardiovascular Diseases Cardiovascular system Carotid Arteries Carotid Endarterectomy Cause of Death Cells Chlorhexidine Chronic Clinical Clinical Management Coagulation Process DNA Dental Dental Care Dental Hygiene Development Disease Disease Marker E-Selectin Ensure Epidemiologic Studies Exposure to Fibrin fragment D Functional disorder Genomics HIV HIV Infections HLA-DR Antigens Health Heart Diseases Hemorrhage Highly Active Antiretroviral Therapy Home environment Hour Human Immune Immune response Immune system Immunity Individual Inflammation Inflammatory Interleukin-6 Intervention Intervention Studies Invaded Irrigation Learning Ligands Link Lipopolysaccharides Measurement Measures Mediating Methodology Microspheres Morbidity - disease rate Observational Study Oral Oral cavity Patients Periodontal Diseases Persons Pilot Projects Plasma Population Predisposing Factor Reporting Research Infrastructure Resources Risk Risk Factors Sample Size Severities Side Site Specimen Staging T-Lymphocyte Testing Thick Thromboplastin Time Tissues Toll-like receptors Tooth structure Variant Visit Vulnerable Populations Work antiretroviral therapy atherogenesis base brachial artery cardiovascular disorder risk clinically relevant clinically significant cohort design experience gluconate heart disease risk high risk immune activation improved indexing inflammatory marker innovation intima media macrophage microbial modifiable risk monocyte mortality neutrophil novel oral infection pathogen public health priorities public health relevance receptor scaling and root planing socioeconomics therapy duration

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is a leading cause of death in HIV-infected adults, with both chronic HIV and sustained use of antiretroviral therapy (ART) contributing to heart disease. Identifying the specific mechanisms and any modifiable risk factors for CVD in this vulnerable population is a public health priority. We hypothesize that HIV-infected patients who are treated for periodontal disease (PD) will show significant improvement in endothelial function and key systemic biomarkers of immunity as compared to their own baseline values. We propose a pre-post observational study of immune, inflammatory, coagulation and vascular consequences following the treatment of severe PD in HIV-infected adults. Severe PD will be defined by A) >30% of teeth with e1 site with periodontal probing depth (PPD) e5 mm in addition to clinical attachment level (CAL) e3.0 mm at these sites and B) bleeding on probing (BOP) at >30% of all sites. Subjects entering the study will receive clinically-indicated intensive periodontal therapy (IPT) consisting of: A) full-mouth scaling and root planing (SC/RP) with subgingival chlorhexidine gluconate (CHX) irrigation at baseline, 1 and 2 months, B) placement of minicycline microspheres in all sites with PPD e4.0 mm after each of three SC/RP visits, C) "hands-on" coaching of targeted oral hygiene improvements, and D) home use of CHX. Successful PD treatment will be defined a-priori as BOP occurring at d10% of sites, no PPD e5.0 mm and d15% of sites with PPD=4.0 mm. Our primary objective is to test whether IPT in immunologically stable HIV-infected adults significantly improves brachial artery flow mediated dilation (FMD) at six months as compared to each individual's baseline FMD value. Our secondary objective is to determine whether systemic biomarkers of inflammation (interleukin 6 and soluble E-selectin), microbial translocation (neutrophils and soluble CD14), coagulation (D-dimers and tissue factor expression on monocytes) and immune activation (%CD38+ HLA-DR+ on CD8+ T-cells) at two months predict improvement in FMD at six months. The primary endpoint is the percent change from baseline in FMD at six months. The secondary endpoint is to investigate the cross-sectional and longitudinal effects of the above biomarkers measured at baseline, 1, 2 and 6 months on FMD. A sample size of 35 patients is needed to detect a 15% change in FMD between baseline and 6 months after baseline with 80% power, based on a two-sided paired t-test and assuming 1) FMD has a lognormal distribution; 2) the coefficient of variation of FMD at each time point is 0.29; 3) the correlation between FMD at baseline and FMD at 6 months is 0.5; and 4) a significance level of 0.05. Assuming a 25% attrition rate, 44 patients will be needed to ensure that 35 patients complete the study. In addition to a lower socioeconomic HIV-infected cohort with poor dental care utilization and high levels of PD, our group has the requisite resources and infrastructure to successfully complete this innovative, highly translational observational study. PUBLIC HEALTH RELEVANCE: Gum disease has been reported to contribute to heart disease and adults with HIV- infection have a higher risk for developing both heart disease and gum disease. We suspect that the effects of gum disease on the immune system promote heart disease. By observing HIV-infected adults before and after an intensive treatment of gum disease, we will see whether immune-related factors within blood improve as a result of treatment and whether this also improves the health of blood vessels. By performing this study, we may discover whether treating gum disease can lower an HIV-infected person's risks for heart disease and we may be able to learn specific details about how the immune system contributes to the risk for heart disease.

描述（由申请人提供）：心血管疾病（CVD）是艾滋病毒感染的成年人的主要死亡原因，患有慢性艾滋病毒和持续使用抗逆转录病毒疗法（ART），导致心脏病。在此脆弱人群中确定CVD的具体机制和任何可修改的风险因素是公共卫生的重点。我们假设接受牙周疾病（PD）治疗的艾滋病毒感染的患者将显示出与自己的基线值相比，内皮功能和关键系统性生物标志物的显着改善。我们提出了一项对HIV感染的成年人严重PD治疗后免疫，炎症，凝结和血管后果的前观察研究。严重的PD将由a）> 30％的牙齿具有E1位点，除临床附着水平（CAL）E5 mm（cal）E30 mm外，在这些部位的临床附着水平（CAL）E5 mm（cal）E5 mm（cal）E30 mm，在所有站点> 30％的探测器上出血（BOP）。进入该研究的受试者将接受临床指示的强化牙周治疗（IPT），包括：a）在基线，1和2个月的尺寸缩放和根平面和根平面策划（SC/RP），并在基线，1和2个月内进行替代氯己定葡萄糖酸（CHX）灌溉（CHX）灌溉，均在所有sc/c）中均访问了ppd e4.0 mmm。 “动手”指导有针对性的口腔卫生改善，d）CHX的家庭使用。成功的PD处理将被定义为A-PRIORI，因为BOP发生在D10％的地点，无PPD E5.0 mM和PPD = 4.0 mm的位点的D15％。我们的主要目的是测试与每个人的基线FMD值相比，在六个月内，在免疫学稳定的HIV感染的成年人IPT是否可以显着改善臂动脉流介导的扩张（FMD）。我们的次要目标是确定炎症的全身生物标志物（白介素6和可溶性E-选择素），微生物易位（中性粒细胞和可溶性CD14），凝结（Dimers和组织因子在单核细胞上的Dimers和组织因子表达）是否是否在CD8+ T-cd8+ T-Cells上进行了六个月的cd38+ HLA-DR+ tw cd8+ T-Cells frm twy+ t ccd8+ t-clys in fra+ t cd8+ t ccd8+ t cy。主要终点是六个月的FMD的基线变化的百分比变化。次要终点是研究基线在FMD上1、2和6个月测得的上述生物标志物的横截面和纵向作用。基于双面配对的t检验和假设1）FMD具有对数正态分布，需要35例患者的样本量以检测基线和基线后6个月之间的FMD变化15％； 2）每个时间点FMD的变化系数为0.29； 3）基线时FMD与6个月时FMD之间的相关性为0.5； 4）显着性水平为0.05。假设损耗率为25％，则需要44名患者，以确保35名患者完成研究。除了较低的社会经济感染的艾滋病毒感染队列，牙齿护理利用率不佳和PD的高水平外，我们的小组还拥有必要的资源和基础设施，可以成功完成这项创新的，高度转化的观察性研究。公共卫生相关性：据报道，牙龈疾病会导致心脏病，艾滋病毒感染的成年人患心脏病和牙龈疾病的风险更高。我们怀疑牙龈疾病对免疫系统的影响促进了心脏病。通过观察对牙龈疾病进行密集治疗前后的HIV感染的成年人，我们将看到血液中与免疫相关的因素是否因治疗而改善，以及这是否还可以改善血管健康。通过进行这项研究，我们可以发现治疗牙龈疾病是否可以降低感染HIV的人患心脏病的风险，并且我们可能能够学习有关免疫系统如何促进心脏病风险的特定细节。