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

Modulation of Iron Deposition in Sickle Cell Disease and Other Hemoglobinopathies SURVEY STUDY

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Thalassemia; Diamond-Blackfan Anemia

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 Type: Observational
• Enrollment (Actual): 423

Contacts and Locations

Study Locations

• Germany
  • Hamburg-Eppendorf, Germany
    • Universitätsklinikum Hamburg-Eppendorf
• United Kingdom
  • London, United Kingdom, WC1E 6BT
    • UCL Cancer Institute
• United States
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital & Research Center Oakland
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Adult Comprehensive Sickle Cell Center, Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson SCD Program
  • Tennessee
    • Memphis, Tennessee, United States, 38105-3678
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

There is no gender predisposition for sickle cell disease, thalassemia major, or Diamond-Blackfan anemia. Sickle cell anemia most frequently affects people of African descent, thalassemia affects people of Mediterranian, northern African, Southeast Asia and Indian descent. Diamond-Blackfan anemia occurs across all racial and ethnic groups.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of iron overloaded patients with Sickle Cell Disease and Thalassemia eligible for future study of iron deposition and biochemical mechanisms	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.	March 2010 - July 2013

Collaborators and Investigators

• Sponsor: UCSF Benioff Children's Hospital Oakland
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Medical University Innsbruck; Universitätsklinikum Hamburg-Eppendorf; University College London (UCL) Cancer Institute
• Investigators: Principal Investigator: John Porter, MD, University College London Cancer Institute

Study record dates

Study Major Dates

• Study Start: March 31, 2010
• Primary Completion (Actual): August 31, 2013
• Study Completion (Actual): October 31, 2013

Study Registration Dates

• First Submitted: July 30, 2013
• First Submitted That Met QC Criteria: July 30, 2013
• First Posted (Estimate): August 1, 2013

Study Record Updates

• Last Update Posted (Actual): September 23, 2020
• Last Update Submitted That Met QC Criteria: September 22, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Red-Cell Aplasia, Pure; Anemia, Sickle Cell; Thalassemia; Anemia, Diamond-Blackfan
• Other Study ID Numbers: 2010-019; 2R01DK057778-06A1 (U.S. NIH Grant/Contract)