NCT01114776

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Nov 2009

Longer than P75 for all trials

Geographic Reach
3 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2009

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

April 30, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 3, 2010

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2013

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2013

Completed
Last Updated

September 24, 2020

Status Verified

September 1, 2020

Enrollment Period

3.7 years

First QC Date

April 30, 2010

Last Update Submit

September 22, 2020

Conditions

Sickle Cell DiseaseThalassemiaDiamond-Blackfan Anemia

Outcome Measures

Primary Outcomes (1)

  • Pilot study of biochemical mechanisms of iron deposition in patients with Sickle Cell Disease, Thalassemia and Diamond-Blackfan Anemia.

    To 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, and finally lower uptake and enhanced export of NTBI by cardiomyocytes conditioned by SCD serum, when compared with similarly iron overloaded patients with beta thalassemia and diamond blackfan anemia.

    March 2010 - August 2012

Secondary Outcomes (4)

  • Comparison of cardiac and pituitary iron content by MRI

    March 2010 - August 2012

  • Characterization of levels and speciation of NTBI in heavily transfused SCD vs. TM (or DBA)

    March 2010 - August 2012

  • 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)

    March 2010 - August 2012

  • 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)

    March 2010 - August 2012

Study Arms (4)

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.

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.

Controls

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-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, 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Children's Hospital & Research Center Oakland

Oakland, California, 94609, United States

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg-Eppendorf, Germany

Location

UCL Cancer Institute

London, WC1E 6BT, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, serum, plasma, and urine

MeSH Terms

Conditions

Anemia, Sickle CellThalassemiaAnemia, Diamond-Blackfan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesAnemia, Hypoplastic, CongenitalAnemia, AplasticRed-Cell Aplasia, PureCongenital Bone Marrow Failure SyndromesBone Marrow Failure DisordersBone Marrow Diseases

Study Officials

  • Elliott Vichinsky, MD

    UCSF Benioff Children's Hospital Oakland

    PRINCIPAL INVESTIGATOR

  • John B Porter, MD

    University College London (UCL) 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

April 30, 2010

First Posted

May 3, 2010

Study Start

November 1, 2009

Primary Completion

July 31, 2013

Study Completion

September 30, 2013

Last Updated

September 24, 2020

Record last verified: 2020-09

Locations

US(1)DE(1)GB(1)