Crizanlizumab Improves Tissue Oxygen Supply Demand Matching in Patients With Sickle Cell Anemia
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 主要终点
- The investigators will test whether SEG101 improves Supply-Demand Matching in patients with sickle cell anemia by measuring the change in tissue oxygenation by near infrared spectroscopy from baseline to 3 months and to 6 months.
研究概览
简要总结
Hypothesis
Efficient unloading of oxygen to regions of high metabolic demand requires a healthy microvasculature to sense local oxygen tension and regulate flow, accordingly. In sickle cell disease patients, the investigators have demonstrated oxygen supply-demand mismatch, or SDM, in proportion to anemia severity. SDM occurs in both the peripheral circulation and the brain, and four characteristics: 1) Hyperemia beyond expected for the level of anemia, 2) Corresponding loss of vascular dilatory reserve, 3) Impaired oxygen unloading to the tissues, and 4) Tissue hypoxia. In sickle cell disease, red blood cell (RBC) and white blood cell (WBC) adhere to vascular endothelium triggering transient or irreversible microvascular damage as well as releasing vasoactive substances that contribute to microvascular dysregulation. The investigators postulate that ongoing microvascular damage/dysregulation in the setting of increased total blood flow contributes to SDM. The investigators believe SEG101, by lowering RBC and WBC adhesion to the microvasculature, will improve SDM and tissue oxygenation.
Objectives
- Primary - The investigators will test whether SEG101 improves SDM in patients with sickle cell anemia by measuring the change in tissue oxygenation measured by near infrared spectroscopy (NIRS).
- Secondary/Exploratory - The investigators will identify end-organ disease and whether improvement of SDM by SEG101 occurs in patients with sickle cell anemia.
详细描述
Objectives Primary Objectives 1. The investigators will test whether SEG101 improves Supply-Demand Matching in patients with sickle cell anemia measured by the change in tissue oxygenation by NIRS.
a) This is measured as a percent oxyhemoglobin saturation (%).
Secondary Objectives
-
Secondary measures to assess the change in tissue oxygenation will be
-
In the somatic peripheral circulation - microcirculatory perfusion at rest and post-ischemia by laser doppler, venous oxygen saturation by venous blood gas and co-oximetry, and vasoconstriction by plethysmography.
-
In the cerebral circulation - blood flow by arterial spin labeling, function brain MRI and response to CO2 challenge, sagittal sinus saturation by TRUST and tissue oxygen extraction by asymmetric spin echo.
-
In the pulmonary vasculature - Pulmonary circulation - sleep study pulse oximetry for oxygenation and vasoconstriction by plethysmography, tricuspid regurgitant jet velocity (TRV) with echo markers of diastolic function to balance pulmonary vascular vs. left heart etiology of TRV.
-
Determine the relationship between SDM biomarkers and hemoglobin level (anemia).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
treatment
The effects of Crizanlizumab will be assessed in 20 nontransfused SCD subjects. After comprehensive baseline assessment one month prior the time of study initiation, patients will be started on 5mg/kg of body weight to be initiated at week 1 with follow up dosing at week 3 and week 7 then q4weeks until week 23, which will be the last dose given (7 total doses). Safety laboratories will be drawn at each infusion visit. There will be a follow up phone call the day after receiving the medication. Comprehensive blood and vascular testing will be repeated at Week 11 and Week 23 of treatment.
干预措施: Crizanlizumab (Drug)
control
A total of 10 SCD subjects will be recruited from the hematology clinic at CHLA, generating a similar distribution of SS and Sß0 hemoglobin. They will be studied twice, once at the beginning of the study, time 0, and once at the end of study, after 6 months. They will undergo the same cerebral, peripheral and cardiopulmonary testing procedures as the patients undergoing therapy. They will also have monthly phone calls to determine clinical outcomes such as crisis frequency, medication use, hospitalizations and other pertinent clinical findings that may arise.
干预措施: control (Other)
结局指标
主要结局
The investigators will test whether SEG101 improves Supply-Demand Matching in patients with sickle cell anemia by measuring the change in tissue oxygenation by near infrared spectroscopy from baseline to 3 months and to 6 months.
时间窗: Change measured over a 23 week period
Tissue oxygenation is measured by near infrared spectroscopy in rSO2%. The investigators will account for changes in microcirculatory perfusion at rest and post-ischemia by laser doppler.
次要结局
- The investigators will test whether SEG101 improves Supply-Demand Matching in patients with sickle cell anemia by measuring the change in microcirculatory perfusion at rest and post-ischemia(Change measured over a 23 week period)
- The investigators will test whether SEG101 improves Supply-Demand Matching in patients with sickle cell anemia by measuring the change in venous blood saturation and change in vessel endothelial function(Change measured over a 23 week period)
- The investigators will test whether SEG101 improves Supply-Demand Matching in patients with sickle cell anemia in the pulmonary vasculature using tricuspid regurgitant jet velocity as an estimate of pulmonary artery pressure.(Change measured over a 23 week period)