Sickle Cell DiseaseMCSIONCT01114776
Multi-Center Study of Iron Overload: Pilot Study
An observational study of Sickle Cell Disease and Thalassemia, run by UCSF Benioff Children's Hospital Oakland at 3 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sickle Cell Disease, Thalassemia, Diamond-Blackfan Anemia
- How many people
- 20 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 1 Nov 2009to 30 Sep 2013
- 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 16 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
Children's Hospital & Research Center Oakland
Oakland, California, 94609
About this 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
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.
Read the 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.
- Conditions
- Sickle Cell Disease, Thalassemia, Diamond-Blackfan Anemia
- Medical subject headings
- Anemia, Sickle Cell, Thalassemia, Anemia, Diamond-Blackfan
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 |
|---|---|---|
| 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 | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: March 2010 - August 2012
Secondary outcomes (4)
Comparison of cardiac and pituitary iron content by MRI
We will measure cardiac and pituitary iron deposition by MRI in SCD with 10-20 years of transfusion exposure (0.2-0.6 mg Fe/kg/day) and compare this to measurements in a similarly transfused group of TM (or DBA). Patients with similar duration of chronic transfusion and age at onset of chronic transfusion therapy will be compared.
Measured: March 2010 - August 2012
Characterization of levels and speciation of NTBI in heavily transfused SCD vs. TM (or DBA)
Levels of total and speciated NTBI (directly chelatable, labile plasma (LPI) and bleomycin-reactive) will be correlated with inflammatory biomarkers, hepcidin levels and organ iron deposition in patients with SCD, TM (or DBA). Results from the 3 patient populations will be compared to determine the possible effect of ineffective erythropoiesis in TM on the amount or species of NTBI present in the circulation.
Measured: 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)
To examine the hypothesis that disease-related differences in inflammatory markers, hepcidin, and nutritional factors affect NTBI deposition, we will define the relationships between plasma and monocyte cytokines known to have cellular effects on iron cell trafficking (IL-1, IL-6, IL-10, TNFalpha, and TGFbeta), hepcidin concentration, and nutrient factors on NTBI levels and characteristics.
Measured: 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)
We will examine iron homeostasis in primary monocytes obtained from the 4 study groups to ascertain whether there is increased iron accumulation in monocytes in SCD patients. We will determine total cellular iron and ferritin-bound iron in monocytes isolated from the blood of SCD, TM and DBA patients.
Measured: March 2010 - August 2012
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2010 (estimated)
- Study start1 Nov 2009
- Primary completion31 Jul 2013
- Study completion30 Sep 2013
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.
- 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-control
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCSF Benioff Children's Hospital Oakland
- Sponsor type
- University, hospital or other
- Collaborators
- University College London (UCL) Cancer Institute, Universitätsklinikum Hamburg-Eppendorf, Medical University Innsbruck, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Elliott Vichinsky, MD, Principal investigator, UCSF Benioff Children's Hospital OaklandJohn B Porter, MD, Principal investigator, University College London (UCL) Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01114776
- Sponsor's protocol ID
- 2009-068
- Other IDs
- R01DK057778-06A1
- Acronym
- MCSIO
- Status last verified
- Sep 2020
- First submitted
- 30 Apr 2010
- Last updated
- 24 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study Examining Mechanisms of Iron Trafficking and Extra-hepatic Iron Distribution in Sickle Cell Disease, Thalassemia, and Other Iron Loading Anemias
- ClinicalTrials.gov ID
- NCT01114776
- Acronym / sponsor ID
- MCSIO / 2009-068
- Conditions
- Sickle Cell Disease, Thalassemia, Diamond-Blackfan Anemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- UCSF Benioff Children's Hospital OaklandUniversity, hospital or other
- Collaborators
- University College London (UCL) Cancer Institute, Universitätsklinikum Hamburg-Eppendorf, Medical University Innsbruck, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Nov 2009
- Primary completion
- 31 Jul 2013 (actual)
- Study completion
- 30 Sep 2013 (actual)
- First posted
- 3 May 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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 | – | – |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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;
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
Pilot study of biochemical mechanisms of iron deposition in patients with Sickle Cell Disease, Thalassemia and Diamond-Blackfan Anemia.
Time frame: March 2010 - August 2012
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.
4 secondary outcomes
Comparison of cardiac and pituitary iron content by MRI
Time frame: March 2010 - August 2012
Characterization of levels and speciation of NTBI in heavily transfused SCD vs. TM (or DBA)
Time frame: 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)
Time frame: 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)
Time frame: March 2010 - August 2012
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 24 Sep 2020.
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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.
Elliott Vichinsky, MD principal investigator
UCSF Benioff Children's Hospital Oakland
John B Porter, MD principal investigator
University College London (UCL) Cancer Institute
3 sites in 3 countries: 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 UCSF Benioff Children's Hospital Oakland at 3 sites in 3 countries.
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 3 inclusion and 7 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 24 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Germany, United Kingdom. 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?
Pilot study of biochemical mechanisms of iron deposition in patients with Sickle Cell Disease, Thalassemia and Diamond-Blackfan Anemia. (time frame: March 2010 - August 2012). 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 24 Sep 2020.