Clinical trial NCT01114776: Multi-Center Study of Iron Overload: Pilot Study
Official title: Pilot Study Examining Mechanisms of Iron Trafficking and Extra-hepatic Iron Distribution in Sickle Cell Disease, Thalassemia, and Other Iron Loading Anemias
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: 2010-05-03
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
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 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.

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

Primary outcomes:
measure: Pilot study of biochemical mechanisms of iron deposition in patients with Sickle Cell Disease, Thalassemia and Diamond-Blackfan Anemia.
timeFrame: March 2010 - August 2012
Secondary outcomes:
measure: Comparison of cardiac and pituitary iron content by MRI
timeFrame: March 2010 - August 2012
measure: Characterization of levels and speciation of NTBI in heavily transfused SCD vs. TM (or DBA)
timeFrame: March 2010 - August 2012
measure: 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)
timeFrame: March 2010 - August 2012
measure: 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)
timeFrame: March 2010 - August 2012
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland
state: California
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 (UCL) Cancer Institute
name: John B Porter, MD
role: PRINCIPAL_INVESTIGATOR
References: