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

Completed
Conditions
Sickle Cell Disease
Thalassemia
Diamond-Blackfan Anemia
Registration Number
NCT01913548
Lead Sponsor
UCSF Benioff Children's Hospital Oakland
Brief Summary

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.

Detailed 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
423
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Identification of iron overloaded patients with Sickle Cell Disease and Thalassemia eligible for future study of iron deposition and biochemical mechanismsMarch 2010 - July 2013

Patients with similar duration of chronic transfusion and age at onset of chronic transfusion therapy will be identified from 10 participating centers. Detailed information on iron burden and transfusion, medical, and chelation histories will be obtained in order to establish a cohort of patients that could be available for a future powered study of extra-hepatic iron deposition and underlying biochemical mechanisms.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (8)

Children's Hospital & Research Center Oakland

🇺🇸

Oakland, California, United States

Georgia Regents University

🇺🇸

Augusta, Georgia, United States

Thomas Jefferson SCD Program

🇺🇸

Philadelphia, Pennsylvania, United States

Adult Comprehensive Sickle Cell Center, Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Children's Memorial Hospital

🇺🇸

Chicago, Illinois, United States

UCL Cancer Institute

🇬🇧

London, United Kingdom

Universitätsklinikum Hamburg-Eppendorf

🇩🇪

Hamburg-Eppendorf, Germany

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

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