Multi-Center Study of Iron Overload: Pilot Study

NCT ID: NCT01114776

Last Updated: 2020-09-24

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-11-01
• Study Completion Date: 2013-09-30

Brief 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.

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.

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.

Conditions

Sickle Cell Disease; Thalassemia; Diamond-Blackfan Anemia

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

Controls

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University College London (UCL) Cancer Institute

OTHER

Sponsor Role: collaborator

Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role: collaborator

Medical University Innsbruck

OTHER

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

UCSF Benioff Children's Hospital Oakland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elliott Vichinsky, MD

Role: PRINCIPAL_INVESTIGATOR

UCSF Benioff Children's Hospital Oakland

John B Porter, MD

Role: PRINCIPAL_INVESTIGATOR

University College London (UCL) Cancer Institute

Locations

Children's Hospital & Research Center Oakland

Oakland, California, United States

Universitätsklinikum Hamburg-Eppendorf

Hamburg-Eppendorf, , Germany

UCL Cancer Institute

London, , United Kingdom

Countries

United States; Germany; United Kingdom

Other Identifiers

R01DK057778-06A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2009-068

Identifier Type: -

Identifier Source: org_study_id