Sickle cell disease
Conditions
Interventions
Once daily deferasirox, starting with the lowest dose of 360 mg per day during 6 weeks
Sponsors
Amsterdam UMC location AMC.
Eligibility
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1. High performance liquid chromatography confirmed diagnosis of HbSS or HbSß0 geno-type. 2. Aged 18-65 years 3. Written informed consent
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. Blood transfusion in the preceding four months 2. Already using iron chelation due to iron overload 3. Ferritin levels of <50 µg/L and/or transferrin saturation of < 0.20. 4. LDH of < 300 U/L 5. Pregnancy or the desire to get pregnant in the following 6 months 6. Impaired renal function of GFR < 60 ml/min/1,73m2 (CKD-EPI). 7. Known allergic reaction to deferasirox. 8. Other somatic or cognitive condition disturbing adherence to study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - To assess efficacy of treatment with deferasirox on sickling as evaluated by change in Point of Sicking (PoS, expressed in mmHg), as quantified by the Oxygenscan. Maximum efficacy is defined as the lowest PoS measured during the treatment period relative (%) to the mean PoS at baseline (before treatment). - To evaluate safety of deferasirox (signs of iron or other electrolyte deficiency), relationship of deferasirox to AE and SAE; number of medication discontinuations. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To evaluate RBC degradation as expressed by phosphatidylserine (PS) exposure on the outer surface of RBC membrane and markers of hemolysis (cell-free heme, lactate dehydrogenase (LDH), bilirubin, reticulocytes and hemoglobin - To evaluate the effect of deferasirox on RBC HbS percentage - Effect of deferasirox on levels of non-transferrin bound iron (NTBI) and labile plasma iron (LPI). - To evaluate the effect of deferasirox on oxidative stress as expressed by intracellular metabolomics and by plasma levels of AGEs - To evaluate the effect of deferasirox on in vitro adhesion of RBCs - To evaluate the effect of deferasirox on endothelial activation as reflected by plasma levels of soluble vascular adhesion molecule-1 (sVCAM-1) and von Willebrand factor antigen (VWF:Ag) - To evaluate the effect of deferasirox on neutrophil activation as measured with flow cytometry and in vitro NET formation | — |
Contacts
Public ContactAafke Gaartman
Amsterdam University Medicalcenter, location AMC
Outcome results
None listed