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

NCT05392101 | Completed Phase 2 DMC

• 1 other identifier: 2021_007
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (2)

• Point of sickling

  Point of sickling measures by oxygen scan. To measure deformability of Red Blood Cells in shear stress, during oxygen-depletion

  4 months up to 8 months

• Oxidative stress

  Oxidative stress measured by AGES

  4 months up to 8 months

Study Arms (1)

Patient group: 360mg deferasirox

EXPERIMENTAL

Patient group receiving treatment

Drug: Deferasirox 360 MG

Interventions

Deferasirox 360 MG DRUG

Deferasirox 360 MG p.o. once daily

Also known as: Exjade

Patient group: 360mg deferasirox

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• High performance liquid chromatography confirmed diagnosis of HbSS or HbSβ0 genotype.
• Aged 18-65 years
• Written informed consent

You may not qualify if:

• Blood transfusion in the preceding four months
• Already using iron chelation due to iron overload
• Ferritin levels of \<50 µg/L and/or transferrin saturation of \< 0.20.
• LDH of \< 300 U/L
• Pregnancy or the desire to get pregnant in the following 6 months
• Impaired renal function of GFR \< 60 ml/min/1,73m2(CKD-EPI), or chronic medication that influences renal function
• Known allergic reaction to deferasirox.
• Other somatic or cognitive condition disturbing adherence to study treatment

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdan UMC location AMC

Amsterdam, Meibergdreef 9, 1105 AZ, Netherlands

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Erfan Nur, MD, PHD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Phase II open label interventional pilot study. It is a mono-center cohort study

Study Record Dates

• First Submitted: January 25, 2022
• First Posted: May 26, 2022
• Study Start: July 20, 2021
• Primary Completion: August 20, 2022
• Study Completion: November 20, 2022
• Last Updated: February 13, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)