Low Dose Iron Chelation as TReatment of Oxidative Damage in Sickle Cell Disease

• Status: Recruiting
• Trial end date: 2022-11-20
• Target enrollment: 0
• Participant gender: All

Summary

Objective:

To study the safety and efficacy of deferasirox as treatment of oxidative stress in adult subjects with sickle cell disease.

Endpoints:

The investigators will determine whether treatment with iron chelators results in decreased sickling of RBCs, oxidative stress, neutrophil activation, inflammation, endothelial activation and hypercoagulability and ultimately reduced disease severity. If the hypothesis is confirmed in this pilot dose-finding study, a larger randomized controlled clinical trial will be initiated.

Study design:

This will be an open-label pilot study, including 12 patients per dose group with a maximum of 3 dose groups. As the antioxidant capacity of deferasirox might be dose-dependent, the investigators will start with the highest dose of deferasirox (360 mg) deemed adequate for chronic use without causing iron depletion in adult SCD patients.

Study population:

Adult patients with sickle cell anemia (HbSS) or HbS-β0-thalassemia (HbSβ0-thal) visiting the outpatient-clinic of the Academic Medical Center, Amsterdam will be asked for inclusion in the study.

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

Details

• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Treatments: Deferasirox

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 HbSβ0 genotype.

2. Aged 18-65 years

3. Written informed consent

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), or chronic medication that influences renal function

7. Known allergic reaction to deferasirox.

8. Other somatic or cognitive condition disturbing adherence to study treatment