Overview

This trial is active, not recruiting.

Conditions sickle cell disease, thalassemia, diamond-blackfan anemia
Sponsor Children's Hospital & Research Center Oakland
Collaborator University College London (UCL) Cancer Institute
Start date November 2009
End date July 2013
Trial size 20 participants
Trial identifier NCT01114776, 2009-068, R01DK057778-06A1

Summary

The purpose of this study is to initiate pilot studies to demonstrate that a sufficient number of iron-overloaded thalassemia, SCD and DBA populations with similar duration of chronic transfusion, and age at start of transfusions would be available for a confirmatory study and to validate that proposed multicenter MRI and biochemical studies can be completed. The study will 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model case control
Time perspective prospective
Arm
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.
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.
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.

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
Comparison of cardiac and pituitary iron content by MRI
time frame: March 2010 - August 2012
Characterization of levels and speciation of NTBI in heavily transfused SCD vs. TM (or DBA)
time frame: March 2010 - August 2012
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 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

Eligibility Criteria

Male or female participants at least 16 years old.

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, TM 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

Additional Information

Official title Pilot Study Examining Mechanisms of Iron Trafficking and Extra-hepatic Iron Distribution in Sickle Cell Disease, Thalassemia, and Other Iron Loading Anemias
Principal investigator Elliott Vichinsky, MD
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. 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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2013.
Information provided to ClinicalTrials.gov by Children's Hospital & Research Center Oakland.