Sickle Cell DiseaseNCT01239901
Iron Mediated Vascular Disease in Sickle Cell Anemia Patients
An observational study of Sickle Cell Disease, run by Children's Hospital Los Angeles at 1 site in United States.
Trial summary
The purpose of this research study is to determine the frequency and severity of iron overload in patients with Sickle Cell Anemia and its relationship to blood vessel function. The investigators hypothesize that intermittent transfusions that these patients receive during hospitalizations produces significant iron… Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Sickle Cell Disease
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Oct 2018
- 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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Our large and well-established sickle cell Center has strong ties to the SCD community in a large metropolitan area (Los Angeles), placing us in an ideal position to rapidly accrue sufficient subjects to study the prevalence of iron overload and determine the relation between directly measured iron loading, vascular responsiveness and clinically relevant biomarkers of vascular function.
Who may be able to join
- Age > 13 years
- Documented diagnosis of sickle cell anemia (SS, SC, Sß0, Sß+)
- Transfused no more than 8 times in a year.
Who cannot join
- Cardiac pacemaker, implantable neurostimulator or other MRI incompatible device.
- History of extreme claustrophobia in MRI machine or other reason for inability to do MRI without sedation.
- Inability to be positioned on the MRI table for sufficient time to complete the MRI exams.
- Any medical or psychological condition that, in the opinion of the local investigator, would make it unsafe or ill-advised for the subject to participate.
- Currently not receiving chronic transfusion therapy, defined as greater than 8 transfusions per year.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Los Angeles
Los Angeles, California, 90027
About this study
Official title: Iron-mediated Vascular Disease in Sickle Cell Disease.
The purpose of this research study is to determine the frequency and severity of iron overload in patients with Sickle Cell Anemia and its relationship to blood vessel function. The investigators hypothesize that intermittent transfusions that these patients receive during hospitalizations produces significant iron overload and impairs blood vessel relaxation.
Read the detailed description
Patients with sickle cell anemia often require blood transfusion as part of the treatment for their disease. Each teaspoon of transfused blood contains about 5 mg of iron and the levels of iron in sickle cell patients increase rapidly with each transfusion. While iron is necessary for many bodily functions, too much iron damages blood vessels, liver, hormone producing glands (pancreas, pituitary and thyroid) and the heart. It is important to know how iron damages blood vessels because most of the problems experienced by sickle cell anemia patients (stroke, kidney failure, pulmonary hypertension, heart disease) result from blood vessel damage. In this trial, iron in the liver, pancreas, and kidney will be measured noninvasively by MRI while vascular function will be measured by ultrasound and tissue Doppler. Patients will be recruited primarily from the greater Los Angeles area, although patients from greater distances will be allowed to participate.
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell disease, sickle cell anemia, sickled cells, blood vessel, iron overload
- Medical subject headings
- Anemia, Sickle Cell, Iron Overload
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver iron concentration (LIC), pancreas R2*, and kidney R2*, measured by MRI
Liver iron concentration (LIC) will be used as a surrogate for total body iron, pancreatic iron represents a surrogate for extravascular iron deposition, and renal iron as a surrogate for chronic intravascular hemolysis. In addition, labile plasma iron will be measured in blood plasma.
Measured: 15 min MRI done completed during one time study visit
Secondary outcomes (1)
Vascular function.
Measurements will be done through several procedures: Ultrasound of artery in upper arm, Ultrasound of artery in neck, and blood tests of ascorbate and hydrobiopterins.
Measured: Scheduled during one time study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2010 (estimated)
- Study startDec 2009
- Primary completionOct 2018
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital Los AngelesThe 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
- Cross-sectional
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John C. Wood, Children's Hospital Los Angeles
- Investigators
- John C Wood, MD, PhD, Principal investigator, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01239901
- Sponsor's protocol ID
- 1RC1HL099412-01
- Status last verified
- Jan 2019
- First submitted
- 12 Nov 2010
- Last updated
- 10 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Ballas SK. Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol. 2001 Jan;38(1 Suppl 1):30-6. doi: 10.1016/s0037-1963(01)90058-7.
PubMed 11206959Cheung YF, Chan GC, Ha SY. Effect of deferasirox (ICL670) on arterial function in patients with beta-thalassaemia major. Br J Haematol. 2008 May;141(5):728-33. doi: 10.1111/j.1365-2141.2008.07092.x. Epub 2008 Mar 3.
PubMed 18318756Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, Romeo MA, Forni GL, Gamberini MR, Ghilardi R, Piga A, Cnaan A. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004 Oct;89(10):1187-93.
PubMed 15477202Pakbaz Z, Fischer R, Fung E, Nielsen P, Harmatz P, Vichinsky E. Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients. Pediatr Blood Cancer. 2007 Sep;49(3):329-32. doi: 10.1002/pbc.21275.
PubMed 17554789Schein A, Enriquez C, Coates TD, Wood JC. Magnetic resonance detection of kidney iron deposition in sickle cell disease: a marker of chronic hemolysis. J Magn Reson Imaging. 2008 Sep;28(3):698-704. doi: 10.1002/jmri.21490.
PubMed 18777554Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD, Coates TD. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood. 2005 Aug 15;106(4):1460-5. doi: 10.1182/blood-2004-10-3982. Epub 2005 Apr 28.
PubMed 15860670Wood JC, Enriquez C, Ghugre N, Otto-Duessel M, Aguilar M, Nelson MD, Moats R, Coates TD. Physiology and pathophysiology of iron cardiomyopathy in thalassemia. Ann N Y Acad Sci. 2005;1054:386-95. doi: 10.1196/annals.1345.047.
PubMed 16339687Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007 Feb;18(2):394-400. doi: 10.1681/ASN.2006070802. Epub 2007 Jan 17.
PubMed 17229910Oudit GY, Trivieri MG, Khaper N, Liu PP, Backx PH. Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. J Mol Med (Berl). 2006 May;84(5):349-64. doi: 10.1007/s00109-005-0029-x. Epub 2006 Apr 8.
PubMed 16604332Walter PB, Fung EB, Killilea DW, Jiang Q, Hudes M, Madden J, Porter J, Evans P, Vichinsky E, Harmatz P. Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease. Br J Haematol. 2006 Oct;135(2):254-63. doi: 10.1111/j.1365-2141.2006.06277.x.
PubMed 17010049Kato GJ, Gladwin MT. Evolution of novel small-molecule therapeutics targeting sickle cell vasculopathy. JAMA. 2008 Dec 10;300(22):2638-46. doi: 10.1001/jama.2008.598.
PubMed 19066384Vanhoutte PM, Shimokawa H, Tang EH, Feletou M. Endothelial dysfunction and vascular disease. Acta Physiol (Oxf). 2009 Jun;196(2):193-222. doi: 10.1111/j.1748-1716.2009.01964.x. Epub 2009 Feb 10.
PubMed 19220204Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V, Hazen SL, Vichinsky EP, Morris SM Jr, Gladwin MT. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. 2005 Jul 6;294(1):81-90. doi: 10.1001/jama.294.1.81.
PubMed 15998894Werner ER, Gorren AC, Heller R, Werner-Felmayer G, Mayer B. Tetrahydrobiopterin and nitric oxide: mechanistic and pharmacological aspects. Exp Biol Med (Maywood). 2003 Dec;228(11):1291-302. doi: 10.1177/153537020322801108.
PubMed 14681545Valenti L, Fracanzani AL, Dongiovanni P, Bugianesi E, Marchesini G, Manzini P, Vanni E, Fargion S. Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case-control study. Am J Gastroenterol. 2007 Jun;102(6):1251-8. doi: 10.1111/j.1572-0241.2007.01192.x. Epub 2007 Mar 27.
PubMed 17391316
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Iron-mediated Vascular Disease in Sickle Cell Disease.
- ClinicalTrials.gov ID
- NCT01239901
- Acronym / sponsor ID
- 1RC1HL099412-01
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell disease, sickle cell anemia, sickled cells, blood vessel, iron overload
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Children's Hospital Los AngelesUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Oct 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 15 Nov 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 research study is to determine the frequency and severity of iron overload in patients with Sickle Cell Anemia and its relationship to blood vessel function. The investigators hypothesize that intermittent transfusions that these patients receive during hospitalizations produces significant iron overload and impairs blood vessel relaxation.
Detailed description
Patients with sickle cell anemia often require blood transfusion as part of the treatment for their disease. Each teaspoon of transfused blood contains about 5 mg of iron and the levels of iron in sickle cell patients increase rapidly with each transfusion. While iron is necessary for many bodily functions, too much iron damages blood vessels, liver, hormone producing glands (pancreas, pituitary and thyroid) and the heart. It is important to know how iron damages blood vessels because most of the problems experienced by sickle cell anemia patients (stroke, kidney failure, pulmonary hypertension, heart disease) result from blood vessel damage. In this trial, iron in the liver, pancreas, and kidney will be measured noninvasively by MRI while vascular function will be measured by ultrasound and tissue Doppler. Patients will be recruited primarily from the greater Los Angeles area, although patients from greater distances will be allowed to participate.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Our large and well-established sickle cell Center has strong ties to the SCD community in a large metropolitan area (Los Angeles), placing us in an ideal position to rapidly accrue sufficient subjects to study the prevalence of iron overload and determine the relation between directly measured iron loading, vascular responsiveness and clinically relevant biomarkers of vascular function.
Key inclusion criteria (3 listed)
- Age > 13 years
- Documented diagnosis of sickle cell anemia (SS, SC, Sß0, Sß+)
- Transfused no more than 8 times in a year.
Key exclusion criteria (5 listed)
- Cardiac pacemaker, implantable neurostimulator or other MRI incompatible device.
- History of extreme claustrophobia in MRI machine or other reason for inability to do MRI without sedation.
- Inability to be positioned on the MRI table for sufficient time to complete the MRI exams.
- Any medical or psychological condition that, in the opinion of the local investigator, would make it unsafe or ill-advised for the subject to participate.
- Currently not receiving chronic transfusion therapy, defined as greater than 8 transfusions per year.
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
Liver iron concentration (LIC), pancreas R2*, and kidney R2*, measured by MRI
Time frame: 15 min MRI done completed during one time study visit
Liver iron concentration (LIC) will be used as a surrogate for total body iron, pancreatic iron represents a surrogate for extravascular iron deposition, and renal iron as a surrogate for chronic intravascular hemolysis. In addition, labile plasma iron will be measured in blood plasma.
1 secondary outcome
Vascular function.
Time frame: Scheduled during one time study visit
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 10 Jan 2019.
- Background: PubMed 11206959Ballas SK. Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol. 2001 Jan;38(1 Suppl 1):30-6. doi: 10.1016/s0037-1963(01)90058-7.
- Background: PubMed 18318756Cheung YF, Chan GC, Ha SY. Effect of deferasirox (ICL670) on arterial function in patients with beta-thalassaemia major. Br J Haematol. 2008 May;141(5):728-33. doi: 10.1111/j.1365-2141.2008.07092.x. Epub 2008 Mar 3.
- Background: PubMed 15477202Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, Romeo MA, Forni GL, Gamberini MR, Ghilardi R, Piga A, Cnaan A. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004 Oct;89(10):1187-93.
- Background: PubMed 17554789Pakbaz Z, Fischer R, Fung E, Nielsen P, Harmatz P, Vichinsky E. Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients. Pediatr Blood Cancer. 2007 Sep;49(3):329-32. doi: 10.1002/pbc.21275.
- Background: PubMed 18777554Schein A, Enriquez C, Coates TD, Wood JC. Magnetic resonance detection of kidney iron deposition in sickle cell disease: a marker of chronic hemolysis. J Magn Reson Imaging. 2008 Sep;28(3):698-704. doi: 10.1002/jmri.21490.
- Background: PubMed 15860670Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD, Coates TD. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood. 2005 Aug 15;106(4):1460-5. doi: 10.1182/blood-2004-10-3982. Epub 2005 Apr 28.
- Background: PubMed 16339687Wood JC, Enriquez C, Ghugre N, Otto-Duessel M, Aguilar M, Nelson MD, Moats R, Coates TD. Physiology and pathophysiology of iron cardiomyopathy in thalassemia. Ann N Y Acad Sci. 2005;1054:386-95. doi: 10.1196/annals.1345.047.
- Background: PubMed 17229910Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007 Feb;18(2):394-400. doi: 10.1681/ASN.2006070802. Epub 2007 Jan 17.
- Background: PubMed 16604332Oudit GY, Trivieri MG, Khaper N, Liu PP, Backx PH. Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. J Mol Med (Berl). 2006 May;84(5):349-64. doi: 10.1007/s00109-005-0029-x. Epub 2006 Apr 8.
- Background: PubMed 17010049Walter PB, Fung EB, Killilea DW, Jiang Q, Hudes M, Madden J, Porter J, Evans P, Vichinsky E, Harmatz P. Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease. Br J Haematol. 2006 Oct;135(2):254-63. doi: 10.1111/j.1365-2141.2006.06277.x.
- Background: PubMed 19066384Kato GJ, Gladwin MT. Evolution of novel small-molecule therapeutics targeting sickle cell vasculopathy. JAMA. 2008 Dec 10;300(22):2638-46. doi: 10.1001/jama.2008.598.
- Background: PubMed 19220204Vanhoutte PM, Shimokawa H, Tang EH, Feletou M. Endothelial dysfunction and vascular disease. Acta Physiol (Oxf). 2009 Jun;196(2):193-222. doi: 10.1111/j.1748-1716.2009.01964.x. Epub 2009 Feb 10.
- Individual participant dataSharing planned: No
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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.
John C Wood, MD, PhD principal investigator
Children's Hospital Los Angeles
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, run by Children's Hospital Los Angeles 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 3 inclusion and 5 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 10 Jan 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?
Liver iron concentration (LIC), pancreas R2*, and kidney R2*, measured by MRI (time frame: 15 min MRI done completed during one time study visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01239901, which also lists 25 linked publications.
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 10 Jan 2019.