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

NCT01913548 | Completed

• 2 other identifiers: 2010-0192R01DK057778-06A1
• Study Type: observational
• Target: 423
• Locations: 3 countries
• Sites: 8

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.

Conditions

Sickle Cell Disease; Thalassemia; Diamond-Blackfan Anemia

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

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.

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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);
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• UCSF Benioff Children's Hospital Oakland: lead
• University College London (UCL) Cancer Institute: collaborator
• Universitätsklinikum Hamburg-Eppendorf: collaborator
• Medical University Innsbruck: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (8)

Children's Hospital & Research Center Oakland

Oakland, California, 94609, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Adult Comprehensive Sickle Cell Center, Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Thomas Jefferson SCD Program

Philadelphia, Pennsylvania, 19107, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105-3678, United States

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg-Eppendorf, Germany

Location

UCL Cancer Institute

London, WC1E 6BT, United Kingdom

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Thalassemia; Anemia, Diamond-Blackfan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Elliott Vichinsky, MD

  UCSF Benioff Children's Hospital Oakland

  PRINCIPAL INVESTIGATOR

• John Porter, MD

  University College London Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2013
• First Posted: August 1, 2013
• Study Start: March 31, 2010
• Primary Completion: August 31, 2013
• Study Completion: October 31, 2013
• Last Updated: September 23, 2020

Record last verified: 2020-09

Locations

GB (1); US (6); DE (1)