Multi-Center Study of Iron Overload: Survey Study (MCSIO)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Sickle Cell Disease (SCD) 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) 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) 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. |
Outcome Measures
Primary Outcome Measures
- Identification of iron overloaded patients with Sickle Cell Disease and Thalassemia eligible for future study of iron deposition and biochemical mechanisms [March 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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);
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0 to 9 years old at the initiation of chronic transfusions; no exchange transfusions in the previous 6 months
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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:
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Patients with HbSC, HbS/β thalassemia
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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)
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Presence of any other condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment;
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Any chronic inflammatory illness other than the SCD, THAL or DBA;
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Any acute illness within a 14 day period prior to blood sampling;
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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
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Pregnancy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital & Research Center Oakland | Oakland | California | United States | 94609 |
| 2 | Georgia Regents University | Augusta | Georgia | United States | 30912 |
| 3 | Children's Memorial Hospital | Chicago | Illinois | United States | 60614 |
| 4 | Adult Comprehensive Sickle Cell Center, Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 5 | Thomas Jefferson SCD Program | Philadelphia | Pennsylvania | United States | 19107 |
| 6 | St. Jude Children's Research Hospital | Memphis | Tennessee | United States | 38105-3678 |
| 7 | Universitätsklinikum Hamburg-Eppendorf | Hamburg-Eppendorf | Germany | ||
| 8 | UCL Cancer Institute | London | United Kingdom | WC1E 6BT |
Sponsors and Collaborators
- UCSF Benioff Children's Hospital Oakland
- University College London (UCL) Cancer Institute
- Universitätsklinikum Hamburg-Eppendorf
- Medical University Innsbruck
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
- Principal Investigator: Elliott Vichinsky, MD, UCSF Benioff Children's Hospital Oakland
- Principal Investigator: John Porter, MD, University College London Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2010-019
- 2R01DK057778-06A1