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: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital Los Angeles
• Collaborator: Novartis

Criteria

Inclusion Criteria (Both Patient Groups - 1. SCD on SEG101 and 2. SCD not receiving SEG101)

• We will enroll only SS and Sß0 sickle cell disease patients

• Both male and female will be included.

• Our population of sickle cell disease is 90% African American and 10% Hispanic, therefore, our study population will reflect that distribution of ethnicity.

• Informed consent from legal guardian and/or patient

• Able to participate without needing sedation for MRI scan

• Age at least 16 years

Exclusion Criteria (Both Patient Groups - 1. SCD on SEG101 and 2. SCD not receiving SEG101)

• Any pain crisis requiring an ER visit and/or admission to the hospital and/or required parenteral pain medication in the previous 4 weeks.

• Any acute transfusion in the previous 4 weeks

• Need for chronic transfusion therapy

• Any known chronic illness that in the judgment of the investigator may compromise subject safety or data integrity. These include but are not limited to rheumatologic disorders, malignancy, severe asthma, chronic hepatic or renal insufficiency.

• Known pregnancy

• Seizure disorder

• Inability to cooperate with MRI examinations

• Contraindication to Crizanlizumab