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Genes Influencing Iron Overload State

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ClinicalTrials.gov Identifier: NCT01158794
Recruitment Status : Completed
First Posted : July 8, 2010
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Tracking Information
First Submitted Date July 7, 2010
First Posted Date July 8, 2010
Last Update Posted Date September 18, 2019
Actual Study Start Date September 21, 2010
Actual Primary Completion Date July 31, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 24, 2013)
This study will measure genetic modifiers influencing the iron overload status of patients receiving transfusions. [ Time Frame: Once, at participant enrollment ]
This study will measure the association between GSTM1 gene deletion and other candidate genes and the accumulation and clearance of body iron.
Original Primary Outcome Measures
 (submitted: July 7, 2010)
To investigate the association of GSTM1 gene deletion and liver iron concentration in patients with sickle cell disease and transfusional iron-overload [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures
 (submitted: September 24, 2013)
  • 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 ]
  • 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 ]
  • 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 ]
    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 ]
    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 ]
Original Secondary Outcome Measures
 (submitted: July 7, 2010)
  • 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: 3 years ]
  • 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: 6 years ]
  • 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: 6 years ]
    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: 6 years ]
    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: 6 Years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Genes Influencing Iron Overload State
Official Title Genes Influencing Iron Overload State
Brief Summary

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

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.
Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
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.
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.
Condition
  • Sickle Cell Disease
  • Thalassemia
  • Marrow Aplasia
Intervention Not Provided
Study 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 7, 2010)
50
Original Estimated Enrollment Same as current
Actual Study Completion Date April 17, 2019
Actual Primary Completion Date July 31, 2016   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT01158794
Other Study ID Numbers GENIOS
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party St. Jude Children's Research Hospital
Study Sponsor St. Jude Children's Research Hospital
Collaborators Not Provided
Investigators
Principal Investigator: Jane Hankins, MD, MS St. Jude Children's Research Hospital
PRS Account St. Jude Children's Research Hospital
Verification Date September 2019