Crizanlizumab Improves Tissue Oxygen Supply Demand Matching in Patients With Sickle Cell Anemia
Status:
Not yet recruiting
Trial end date:
2028-07-01
Target enrollment:
Participant gender:
Summary
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.