Clinical trial NCT01913548: Multi-Center Study of Iron Overload: Survey Study (MCSIO)
Official title: Modulation of Iron Deposition in Sickle Cell Disease and Other Hemoglobinopathies SURVEY STUDY
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sickle Cell Disease
Thalassemia
Diamond-Blackfan Anemia
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: University College London (UCL) Cancer Institute
name: Universitätsklinikum Hamburg-Eppendorf
name: Medical University Innsbruck
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2013-08-01
Enrollment: 423
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

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.

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, 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

Primary outcomes:
measure: Identification of iron overloaded patients with Sickle Cell Disease and Thalassemia eligible for future study of iron deposition and biochemical mechanisms
timeFrame: March 2010 - July 2013
Secondary outcomes:
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland
state: California
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Durham
country: United States
facility: Adult Comprehensive Sickle Cell Center, Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson SCD Program
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Hamburg-Eppendorf
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: London
country: United Kingdom
facility: UCL Cancer Institute
Study officials:
affiliation: UCSF Benioff Children's Hospital Oakland
name: Elliott Vichinsky, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University College London Cancer Institute
name: John Porter, MD
role: PRINCIPAL_INVESTIGATOR
References: