Exploring Near Infrared Spectroscopy (NIRS) technologies for assessment of muscle physiology, tissue oxygenation, and blood flow in patients with Sickle Cell Disease (SCD

探索近红外光谱 (NIRS) 技术评估镰状细胞病 (SCD) 患者的肌肉生理学、组织氧合和血流

• 批准号: 10929214
• 负责人: Swee Lay Thein
• 金额: $ 98.68万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10929214
• 关键词: Abnormal Hemoglobins; Acute; Adopted; Affect; African American; African ancestry; Amino Acids; Biological Markers; Birth; Blood Vessels; Blood flow; Cardiovascular system; Cerebrum; Chest; Chronic; Clinical; Data; Devices; Disease; Echocardiography; Enrollment; Erythrocytes; Ethnic Origin; Evaluation; Exercise; Glutamic Acid; Hemoglobin; Hemoglobinopathies; Hemolysis; Hemolytic Anemia; Hypoxia; Impairment; Individual; Inflammation; Inherited; Kidney; Lead; Literature; Longevity; Measurement; Minority Groups; Monitor; Near-Infrared Spectroscopy; Optics; Organ; Outcome; Outpatients; Participant; Patients; Physiological; Polymers; Protocols documentation; Recurrence; Reperfusion Injury; Reporting; Science; Shapes; Sickle Cell; Sickle Cell Anemia; Site; Structure; Techniques; Technology Assessment; Testing; Tissues; United States; Valine; Variant; Vascular Diseases; Vascular Endothelium; Visit; Walking; beta Globin; chronic pain; clinical application; clinical center; endothelial dysfunction; hemodynamics; hemoglobin AA; malignant breast neoplasm; muscle physiology; point of care; research study; response; screening; sickling; tissue oxygenation; vaso-occlusive crisis; vaso-occlusive pain

Sickle cell disease (SCD) is an inherited hemoglobinopathy that disproportionately impacts minority populations in the United States affecting about 100,000 individuals, primarily of African ancestry, and 1 in 365 African-American births. The substitution of valine by glutamic acid on the 6th amino-acid of beta globin results an abnormal hemoglobin variant (HbS) which polymerizes once deoxygenated, and alters both the structure and function of red blood cells (RBCs) distorting them into bizarre sickle shapes. Sickled RBCs have a lifespan 1/6th that of normal, resulting in chronic hemolytic anemia; they are also rigid and can obstruct microvascular blood flow causing recurring, unpredictable cycles of acute vaso-occlusive pain, commonly referred to as vaso-occlusive crises (VOC). The recurrent VOCs lead to hypoxia-reperfusion injury and together with the intravascular hemolysis promote inflammation and vascular endothelial damage. This systemic vasculopathy affects multiple organs leading to cardiovascular complications, chronic pain, cerebral and kidney impairment. Near infrared spectroscopy (NIRS) is a non-invasive optical technique for characterizing microvascular hemodynamics including hemoglobin concentration, blood flow, and tissue oxygen saturation. There is a wealth of literature reporting on NIRS in a wide variety of clinical applications including breast cancer and exercise science. Given the impairments to microvascular flow and endothelial dysfunction associated with SCD, advanced quantitative NIRS is an attractive candidate to provide comprehensive hemodynamic evaluations in point-of-care settings. There are limited studies evaluating NIRS devices in SCD. One study has reported a relatively dampened hyperemic response after brachial cuff occlusion, indicative of endothelial dysfunction in SCD patients. The preliminary data obtained from another research study are encouraging and demonstrates that hemodynamic information collected correlates with clinical lab values. In this single site, non-interventional, exploratory study, 40 subjects (20 SCD (HbSS and/or HbSB0) and 20 healthy controls (HbAA)) will undergo a baseline hemodynamic assessment as outpatients utilizing NIRS applications and protocols. A subset of study participants may be invited to return to the Clinical Center for clinical and NIRS reassessment periodically for a maximum of 4 additional visits, at least 3 days apart, within 120 days from their initial (baseline) visit to test for repeatability of the NIRS. The purpose of this study is to generate further NIRS-derived tissue hemodynamic data in SCD compared to data from healthy controls. The data will help inform the most appropriate and efficient optical technique that best differentiate the abnormal hemodynamics in SCD patients from normal physiological variation in healthy controls. The optimal NIRS technique can then be adopted and applied for regular screening and disease monitoring in SCD patients. To date, There has been a total of 19 subjects enrolled (13 SCD and 6 HbAA)

镰状细胞疾病（SCD）是一种遗传性血红蛋白病，对美国影响约100,000个人，主要是非洲血统的人，而365名非裔美国人出生的人则影响少数群体。谷氨酸在β球蛋白的第六氨基酸中取代缬氨酸会导致异常的血红蛋白变体（HBS），一旦脱氧，它会聚集，并改变了红细胞（RBC）的结构和功能，使它们变成了奇怪的镰刀造型。镰状的RBC的寿命为正常的1/6，导致慢性溶血性贫血。它们也是刚性的，会阻塞微血管血流，从而导致急性血管骨髓性疼痛的反复发生，不可预测的周期，通常称为血管熟悉的危机（VOC）。复发性VOC会导致缺氧 - 再灌注损伤，并与血管内溶血一起促进炎症和血管内皮损伤。这种系统性的血管疾病会影响多个器官，导致心血管并发症，慢性疼痛，大脑和肾脏障碍。 近红外光谱（NIRS）是一种非侵入性光学技术，用于表征包括血红蛋白浓度，血流和组织氧饱和度在内的微血管血液动力学。在包括乳腺癌和运动科学在内的各种临床应用中，有大量有关NIRS的文献报道。鉴于与SCD相关的微血管流量和内皮功能障碍的损害，高级定量NIRS是在护理点环境中提供全面血液动力学评估的有吸引力的候选者。评估SCD中NIRS设备的研究有限。一项研究报道了臂袖闭塞后相对衰减的高血症反应，表明SCD患者的内皮功能障碍。从另一项研究获得的初步数据令人鼓舞，并证明收集的血液动力学信息与临床实验室值相关。 在这个单个部位，非差异，探索性研究，40名受试者（20个SCD（HBSS和/或HBSB0）和20个健康对照（HBAA）（HBAA）将接受基线血液动力学评估，利用NIRS的应用和方案，作为门诊病人。 可以邀请一部分研究参与者返回临床中心进行临床和NIRS的重新评估，最多额外4次访问，至少相隔3天，自初次（基线）访问以来，以测试NIRS的重复性。 这项研究的目的是与健康对照组的数据相比，在SCD中产生进一步的NIRS衍生的组织血流动力学数据。这些数据将有助于告知最合适，最有效的光学技术，从而最好地将SCD患者异常血液动力学与健康对照中的正常生理变异区分开。然后，可以采用最佳NIRS技术，并应用SCD患者的常规筛查和疾病监测。迄今为止，总共有19名受试者（13个SCD和6 HBAA）