Sickle Cell DiseaseNCT01158794
Genes Influencing Iron Overload State
An observational study of Sickle Cell Disease and Thalassemia, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Sickle Cell Disease, Thalassemia, Marrow Aplasia
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Sep 2010to 17 Apr 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
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
Read the 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.
- Conditions
- Sickle Cell Disease, Thalassemia, Marrow Aplasia
- Keywords
- Iron overload, Blood Transfusion
- Medical subject headings
- Anemia, Sickle Cell, Thalassemia, Iron Overload
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
This study will measure genetic modifiers influencing the iron overload status of patients receiving transfusions.
This study will measure the association between GSTM1 gene deletion and other candidate genes and the accumulation and clearance of body iron.
Measured: Once, at participant enrollment
Secondary outcomes (5)
To explore the role of other iron metabolism-associated candidate genes on liver iron concentration of sickle cell patients with transfusional iron-overload.
Measured: 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.
Measured: 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.
Decline of iron concentration is in the heart, pancreas, kidneys, and spleen.
Measured: Once at baseline compared to 3 years after participant enrollment
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.
Decline of iron concentration in the liver, heart, pancreas, kidneys, and spleen of non-sickle cell patients with transfusional iron-overload.
Measured: Once at baseline compared to 3 years after participant enrollment
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.
Measured: Once at baseline compared to 3 years after participant enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2010 (estimated)
- Study start21 Sep 2010
- Primary completion31 Jul 2016
- Study completion17 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jane Hankins, MD, MS, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01158794
- Sponsor's protocol ID
- GENIOS
- Status last verified
- Sep 2019
- First submitted
- 7 Jul 2010
- Last updated
- 18 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genes Influencing Iron Overload State
- ClinicalTrials.gov ID
- NCT01158794
- Acronym / sponsor ID
- GENIOS
- Conditions
- Sickle Cell Disease, Thalassemia, Marrow Aplasia
- Keywords
- Iron overload, Blood Transfusion
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- 21 Sep 2010 (actual)
- Primary completion
- 31 Jul 2016 (actual)
- Study completion
- 17 Apr 2019 (actual)
- First posted
- 8 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
5 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2019.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jane Hankins, MD, MS principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease and Thalassemia, run by St. Jude Children's Research Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
This study will measure genetic modifiers influencing the iron overload status of patients receiving transfusions. (time frame: Once, at participant enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2019.