The Role of Red Cell Characteristics, Angiogenesis, Viscosity and Oxygenation in the Pathophysiology of Sickle Cell Related Retinopathy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Differences in Angiogenesis biomarkers
研究概览
简要总结
Objective:
to gain insight in the pathogenesis, to identify biomarkers to recognize patients at risk for proliferative SCR and to investigate its associations with clinical and laboratory characteristics.
Endpoints:
The investigators will determine the difference in the above named parameters between patients with and without PSCR
Study design:
This case control study will include adult sickle cell disease patients with the HbSS or HbSC genotype. For both genotypes, 20 patients without sickle cell retinopathy (SCR) and 20 patients with PSCR will be included, resulting in a total of 80 patients. Venous blood samples and retinal imaging scans will be collected for each included patient.
详细描述
Rationale:
Sickle cell disease (SCD) is characterized by chronic hemolysis and recurrent microvascular occlusion, resulting in ischemia and organ damage1. This study focuses on retinal damage: sickle cell retinopathy (SCR). SCR results from ischemic vascular disease and secondary angiogenesis, but it is unknown which factors play a significant role in the pathogenesis. Studies on this subject are still in an early phase3,4. Our aim is to gain insight in the pathogenesis, to identify biomarkers to recognize patients at risk for proliferative SCR and to investigate its associations with clinical and laboratory characteristics. The focus of our study is aimed at evaluation of innovative biomarkers of angiogenesis, whole blood viscosity and innovative characterization of red blood cell parameters such as deformability, adhesiveness and "point of sickling" as can be measured ex vivo by the Oxygenscan (i.e.: red cell sickling capacity). The Oxygenscan is a new method to calculate the deformability of red blood cells as a function of the partial pressure of oxygen. These novel parameters will be related to clinical characteristics observed in these patients and specific markers of early retinopathy such as vessel density and macula thinning assessed by OCT angiography.
Objective:
The objective of this study is to gain insight in the pathogenesis, to identify the role of red cell characteristics, markers of angiogenesis, retinal oxygenation and whole blood viscosity in the development of proliferative SCR and to investigate its associations with clinical and laboratory characteristics.
Study design:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Minimum age of 18 years
- •HbSC or HbSS genotype
- •Recent ophthalmologic examination (up to 2 years prior) or (willingness to attend) upcoming examination
排除标准
- •Age below 18 years
- •Genotype other than HbSC or HbSS
- •No recent ophthalmologic examination and no intention to visit the outpatient clinic for ophthalmic and hematologic examination
- •Participation in trials with either crizanlizumab, voxelotor or mitapivat.
结局指标
主要结局
Differences in Angiogenesis biomarkers
时间窗: Immediately after the venepuncture
The difference in plasma levels of parameters representing the level of systemic angiogenesis activity (CD105, VEGF, CTGF and angiopoietin-2) between patients with and without PSCR in both genotypes
Differences in Whole blood viscosity
时间窗: Immediately after the venepuncture
The difference in whole blood viscosity between patients with and without PSCR in both genotypes
Differences in Red blood cell characteristics (Oxygenscan)
时间窗: Immediately after the venepuncture
The difference in red blood cell characteristics (point of sickling) between patients with and without PSCR in both genotypes
Differences in Retinal Oxygenation
时间窗: Immediately after the venepuncture
The difference in oxygenation of the retina by assessing the vessel density with angio- OCT and by assessing the oxygen saturation in the retinal arterioles and venules with the Oxymap scan in patients with and without PSCR in both genotypes
次要结局
- Associations between Oxygenation parameters and Red blood cell characteristics(Immediately after the venepuncture)
- Associations between sex, age, and genotype and the biomarkers of angiogenesis(Immediately after the venepuncture)
- Associations between whole blood viscosity and genotype(Immediately after the venepuncture)
- Association between hemoglobin, and HbF and biomarkers of angiogenesis(Immediately after the venepuncture)
研究者
Bart J. Biemond
Prof. Dr. B.J. Biemond, MD PhD
Amsterdam UMC, location AMC