Multi-Center Study of Iron Overload: Pilot Study (MCSIO)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01114776|
Recruitment Status : Unknown
Verified July 2013 by Elliott Vichinsky, Children's Hospital & Research Center Oakland.
Recruitment status was: Active, not recruiting
First Posted : May 3, 2010
Last Update Posted : July 31, 2013
|Condition or disease|
|Sickle Cell Disease Thalassemia Diamond-Blackfan Anemia|
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.
MRI will be performed measuring pituitary, cardiac, and liver iron.
Laboratory samples should be obtained pre-transfusion and mid-cycle.
All interviews, exams, laboratory tests, study procedures and MRI assessments should be completed within a 0 to 12 weeks time span.
In addition, a healthy control group will also be recruited with similar age, gender, and ethnicity as the disease groups.
|Study Type :||Observational|
|Actual Enrollment :||20 participants|
|Observational Model:||Case Control|
|Official Title:||Pilot Study Examining Mechanisms of Iron Trafficking and Extra-hepatic Iron Distribution in Sickle Cell Disease, Thalassemia, and Other Iron Loading Anemias|
|Study Start Date :||November 2009|
|Actual Primary Completion Date :||July 2013|
|Estimated Study Completion Date :||September 2013|
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 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.
- Pilot study of biochemical mechanisms of iron deposition in patients with Sickle Cell Disease, Thalassemia and Diamond-Blackfan Anemia. [ Time Frame: March 2010 - August 2012 ]To examine the hypothesis that a chronic inflammatory state in Sickle Cell Disease (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, and finally lower uptake and enhanced export of NTBI by cardiomyocytes conditioned by SCD serum, when compared with similarly iron overloaded patients with beta thalassemia and diamond blackfan anemia.
- Comparison of cardiac and pituitary iron content by MRI [ Time Frame: March 2010 - August 2012 ]We will measure cardiac and pituitary iron deposition by MRI in SCD with 10-20 years of transfusion exposure (0.2-0.6 mg Fe/kg/day) and compare this to measurements in a similarly transfused group of TM (or DBA). Patients with similar duration of chronic transfusion and age at onset of chronic transfusion therapy will be compared.
- Characterization of levels and speciation of NTBI in heavily transfused SCD vs. TM (or DBA) [ Time Frame: March 2010 - August 2012 ]Levels of total and speciated NTBI (directly chelatable, labile plasma (LPI) and bleomycin-reactive) will be correlated with inflammatory biomarkers, hepcidin levels and organ iron deposition in patients with SCD, TM (or DBA). Results from the 3 patient populations will be compared to determine the possible effect of ineffective erythropoiesis in TM on the amount or species of NTBI present in the circulation.
- To examine mediators of iron trafficking including inflammatory and regulatory cytokines (TNF-α, IL-1, IL-6, IL-10, TGF β), hepcidin, and nutritional factors (Vitamin C and D) in heavily transfused patients with SCD and TM (or DBA) [ Time Frame: March 2010 - August 2012 ]To examine the hypothesis that disease-related differences in inflammatory markers, hepcidin, and nutritional factors affect NTBI deposition, we will define the relationships between plasma and monocyte cytokines known to have cellular effects on iron cell trafficking (IL-1, IL-6, IL-10, TNFalpha, and TGFbeta), hepcidin concentration, and nutrient factors on NTBI levels and characteristics.
- To examine the cellular mechanisms of iron sequestration in the RES and uptake of iron into other iron storage sites in SCD relative to TM (or DBA) [ Time Frame: March 2010 - August 2012 ]We will examine iron homeostasis in primary monocytes obtained from the 4 study groups to ascertain whether there is increased iron accumulation in monocytes in SCD patients. We will determine total cellular iron and ferritin-bound iron in monocytes isolated from the blood of SCD, TM and DBA patients.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01114776
|United States, California|
|Children's Hospital & Research Center Oakland|
|Oakland, California, United States, 94609|
|UCL Cancer Institute|
|London, United Kingdom, WC1E 6BT|
|Principal Investigator:||Elliott Vichinsky, MD||Children's Hospital & Research Center Oakland|
|Principal Investigator:||John B Porter, MD||University College London (UCL) Cancer Institute|