Multi-Center Study of Iron Overload: Survey Study (MCSIO)

UCSF Benioff Children's Hospital Oakland

Status: Completed

Conditions: Thalassemia; Diamond-Blackfan Anemia; Sickle Cell Disease

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT01913548

2010-019

2R01DK057778-06A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The purpose of this study is to demonstrate that a sufficient number of iron-overloaded thalassemia (THAL), Sickle Cell Disease (SCD)and Diamond Blackfan Anemia (DBA) populations with similar duration of chronic transfusion, and age at start of transfusions would be available for a confirmatory study. The study will examine the hypothesis that a chronic inflammatory state in SCD leads to hepcidin- and cytokine-mediated iron withholding within the RES (reticuloendothelial system), lower plasma NTBI (non-transferrin bound iron) levels, less distribution of iron to the heart in SCD.

Full description

A detailed iron burden, transfusion and chelation history will be obtained from chart review or from participant recall.

Iron burden data will include: 1) documentation of liver iron, and 2) average annual ferritin values.

Transfusion data will include: (1) age at onset of regular transfusions, (2) years of chronic transfusion therapy, and (3) pre-transfusion Hb calculated as average of all assessments for each year.

Enrollment: 423 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 10-20 years of transfusion (defined as 0.2-0.6mg Fe/kg/day exposure with annual ferritin levels greater than 2500 in at least 60% of years of chronic transfusion);
• 0 to 9 years old at the initiation of chronic transfusions; no exchange transfusions in the previous 6 months
• iron overload documented by either liver biopsy, MRI or SQUID with estimated LIC of greater than 7 mg/g dry wt in the previous 6 months or ferritin level greater than 1500mg/dl.

Exclusion criteria

• Patients with HbSC, HbS/β thalassemia
• Pacemaker (active or inactive) or other implanted magnetic devices, severe claustrophobia, or other contraindications to MRI; Unable to remove ferro-magnetic objects from the body in regions to be imaged (e.g., jewelry or piercing)
• Presence of any other condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment;
• Any chronic inflammatory illness other than the SCD, THAL or DBA;
• Any acute illness within a 14 day period prior to blood sampling;
• Patients receiving intensive chelation in the 6 months prior to enrollment including deferoxamine 24 hours per day, 7 days per week or combination treatment with 2 chelators
• Pregnancy

Trial design

423 participants in 3 patient groups

Sickle Cell Disease (SCD)

Description:

Patients with sickle cell diseases, 16 years or older with 10-20 years of transfusion (defined as 0.2-0.6mg Fe/kg/day exposure with annual ferritin levels greater than 2500 in at least 60% of years of chronic transfusion); 0 to 9 years old at the initiation of chronic transfusions; no exchange transfusions in the previous 6 months; and iron overload documented by either liver biopsy, MRI or SQUID with estimated LIC (liver iron content) of greater than 7 mg/g dry wt in the previous 6 months or ferritin level greater than 1500mg/dl.

Thalassemia Major (TM)

Description:

Patients with β-thalassemia major and transfusion-dependent E-beta THAL. 16 years or older with 10-20 years of chronic transfusion (defined above), 0 to 9 years old at the initiation of chronic transfusions, iron overload documented by either liver biopsy, MRI or SQUID with estimated LIC of greater than 7 mg/g dry wt in the previous 6 months.

Diamond Blackfan Anemia (DBA)

Description:

Patients with DBA, 16 years or older with 10-20 years of transfusion, 0 to 9 years old at the initiation of chronic transfusions, iron overload documented by either liver biopsy, MRI or SQUID with estimated LIC of greater than 7 mg/g dry wt in the previous 6 months.