Genes Influencing Iron Overload State

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by St. Jude Children's Research Hospital
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01158794
First received: July 7, 2010
Last updated: October 3, 2014
Last verified: September 2014
  Purpose

Iron overload, which can be defined operationally as too much iron in the body, develops as a consequence of too many blood transfusions given, or due to genetic defects hereditary hemochromatosis). Iron accumulates in several organs in the body, such as the heart, liver, endocrine glands (pancreas, thyroid, etc.), and spleen. Excessive iron can damage organs and may even cause death. Iron overload needs to be appropriately monitored and treated to avoid unnecessary morbidity and mortality.

The present study, GENIOS, proposes to test prospectively the hypothesis that genetic modifiers influence the iron overload status of patients receiving transfusions. To test this hypothesis, the study will perform genetic studies to investigate possible genetic influences for iron accumulation in the body and will study iron accumulation not only in the liver, but also in the heart, pancreas, kidneys, and spleen. In addition: the study will investigate if these same genes have any role during treatment of iron overload, in other words, if certain genetic mutations will influence how iron exits the body. This study will also investigate how substances that are known to control the trafficking of iron in and out of the body and its damaging effects to the tissues (hepcidin and non transferrin-bound iron) are linked to the accumulation of iron in the heart and liver. Iron in the body will be measured by R2*MRI and no liver biopsies will be required. Genetic studies will be done by specialized tests using peripheral blood DNA.

Iron accumulates differently in different people and in different organs of the body. Some people accumulate iron faster than others, even when receiving the same number of blood transfusions


Condition
Sickle Cell Disease
Thalassemia
Marrow Aplasia

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Genes Influencing Iron Overload State

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • This study will measure genetic modifiers influencing the iron overload status of patients receiving transfusions. [ Time Frame: Once, at participant enrollment ] [ Designated as safety issue: No ]
    This study will measure the association between GSTM1 gene deletion and other candidate genes and the accumulation and clearance of body iron.


Secondary Outcome Measures:
  • To explore the role of other iron metabolism-associated candidate genes on liver iron concentration of sickle cell patients with transfusional iron-overload. [ Time Frame: Once, at participant enrollment ] [ Designated as safety issue: No ]
  • To explore the role of GSTM1 genotypes and other iron metabolism-associated candidate genes on maintenance and decline of liver iron concentration of patients with sickle cell disease and transfusional iron-overload. [ Time Frame: Once at baseline compared to 3 years after participant enrollment ] [ Designated as safety issue: No ]
  • Explore the role of GSTM1 genotypes and other iron metabolism-associated candidate genes on increase, maintenance, and decline of iron concentration patients with sickle cell disease and transfusional iron overload. [ Time Frame: Once at baseline compared to 3 years after participant enrollment ] [ Designated as safety issue: No ]
    Decline of iron concentration is in the heart, pancreas, kidneys, and spleen.

  • Explore the role of GSTM1 gene deletion and other iron metabolism-associated candidate genes on increase, maintenance, and decline of iron concentration of non-sickle cell patients* with transfusional iron-overload. [ Time Frame: Once at baseline compared to 3 years after participant enrollment ] [ Designated as safety issue: No ]
    Decline of iron concentration in the liver, heart, pancreas, kidneys, and spleen of non-sickle cell patients with transfusional iron-overload.

  • Explore the relationship between Non-Transferrin Bound Iron (NTBI), hepcidin, organ function, and iron increase, maintenance, and decline in the liver, heart, pancreas, kidneys, and spleen of patients with transfusional iron overload. [ Time Frame: Once at baseline compared to 3 years after participant enrollment ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

The total volume of blood transfused (in ml/kg) will be collected and stored in the study database. Cumulative transfused blood volume (in ml/kg) will be captured. Serum samples will be stored frozen at -20°C until the time of analysis. In addition to the protocol-specific testing of specimens, study participants will be offered the option of allowing any leftover purified DNA, serum, or blood cells to be saved or shared for future analyses. Leftover purified genomic DNA, serum, and blood cells from subjects enrolled in the GENIOS protocol will be de-identified prior to storage or any future testing and/or sharing.


Estimated Enrollment: 50
Study Start Date: August 2010
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Study participants
Participants with sickle cell disease and transfusional iron-overload, and non-sickle cell disease (thalassemia major, cancer patients, etc.) and iron overload. Participants with iron overload, defined as too much iron in the body as a consequence of too many blood transfusions.

Detailed Description:

This study will focus on the following primary objective:

  • To investigate the association of GSTM1 gene deletion and liver iron concentration in patients with sickle cell disease and transfusional iron-overload.

The Secondary Objectives of the study are:

  • To explore the role of other iron metabolism-associated candidate genes on liver iron concentration of sickle cell patients with transfusional iron-overload.
  • To explore the role of GSTM1 genotypes and other iron metabolism-associated candidate genes on maintenance and decline of liver iron concentration of patients with sickle cell disease and transfusional iron-overload.
  • To explore the role of GSTM1 genotypes and other iron metabolism-associated candidate genes on increase, maintenance, and decline of iron concentration in the heart, pancreas, kidneys, and spleen of patients with sickle cell disease and transfusional iron overload.
  • To explore the role of GSTM1 gene deletion and other iron metabolism-associated candidate genes on increase, maintenance, and decline of iron concentration in the liver, heart, pancreas, kidneys, and spleen of non-sickle cell patients with transfusional iron-overload.
  • To explore the relationship between Non-Transferrin Bound Iron (NTBI), hepcidin, organ function, and iron increase, maintenance, and decline in the liver, heart, pancreas, kidneys, and spleen of patients with transfusional iron overload.
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Study participants will be patients who receive medical care at St. Jude Children's Research Hospital and have developed iron overload secondary to multiple transfusions. Patients will be approached during regular outpatient visits and will be invited to participate in this study if they meet the inclusion/exclusion criteria and consent to participate in the study. Non-sickle cell patients with transfusional iron overload includes patients with thalassemia, bone marrow failure syndromes, and patients who have received multiple blood transfusions due to marrow aplasia secondary to the use of chemotherapeutic agents. About 40 participants with sickle cell disease are targeted. About 10 participants with non-sickle cell disease are targeted.

Criteria

Inclusion Criteria:

  • History of ≥ 12 lifetime erythrocyte transfusions who have not yet initiated treatment to unload iron (iron chelation or therapeutic phlebotomy), or
  • History of ≥ 12 lifetime erythrocyte transfusions who have initiated treatment to unload iron, but had liver iron content measurement (by R2*MRI) within 3 months prior to initiation of iron unloading treatment

Exclusion Criteria

  • Known contraindication to performance of MRI (e.g.: presence of MRI-incompatible ferromagnetic material in the body)
  • Prior participation on the St. Jude MRIRON protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01158794

Contacts
Contact: Jane Hankins, MD, MS 1-866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Jane Hankins, MD, MS    866-278-5833    info@stjude.org   
Principal Investigator: Jane Hankins, MD, MS         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Jane Hankins, MD, MS St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01158794     History of Changes
Other Study ID Numbers: GENIOS
Study First Received: July 7, 2010
Last Updated: October 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Iron overload
Blood Transfusion

Additional relevant MeSH terms:
Anemia, Sickle Cell
Thalassemia
Iron Overload
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 19, 2014