Sickle Cell DiseaseNCT03277547
Kidney Function in Sickle Cell Anemia
An observational study of Sickle Cell Disease and Kidney Failure, Chronic, run by Kenneth Ataga MD at 3 sites in United States.
Trial summary
This is a prospective clinical cohort study that involves a baseline study visit followed by up to 3 annual follow-up study visits for a total follow-up of 36-48 months to evaluate the age- and sex-adjusted rate of change in kidney function, and to identify biomarkers of endothelial function, metabolomic profiles and… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sickle Cell Disease, Kidney Failure, Chronic
- How many people
- 300 participants
- Where
- 3 sitesUnited States
- Study dates
- 17 Nov 2017to 1 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with HbSS or HbSB0 thalassemia between the ages of 18 and 65 years who meet the eligibility criteria and provide consent to participate in the study
Who may be able to join
- age of 18 to 65 years;
- confirmed diagnosis of sickle cell anemia (HbSS and SB0 thalassemia);
- non-crisis, "steady state" with no severe pain episodes requiring medical contact during the preceding 4 weeks;
- ability to understand the requirements of the study and be willing to give informed consent.
Who cannot join
- bone marrow transplantation;
- history of long-standing diabetes mellitus with suspicion for diabetic nephropathy as determined by a nephrologist;
- known diagnosis of hepatitis B or C infection (patients will not be screened specifically for this during the study);
- known HIV positive (patients will not be screened specifically for this);
- history of cancer, except non-melanoma skin cancer;
- pregnant or breastfeeding;
Show all 9Show fewer
- connective tissue disease such as SLE;
- known glomerular disease unrelated to SCD;
- patients with ESRD on chronic dialysis.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of North Carolina-Chapel Hill
Chapel Hill, North Carolina, 27599
Ohio State Adult Sickle Cell Program
Columbus, Ohio, 43210
UTHSC Center for Sickle Cell Disease
Memphis, Tennessee, 38163
About this study
Official title: The Association of Biomarkers of Endothelial Function With Prospective Changes in Kidney Function in Sickle Cell Anemia
This is a prospective clinical cohort study that involves a baseline study visit followed by up to 3 annual follow-up study visits for a total follow-up of 36-48 months to evaluate the age- and sex-adjusted rate of change in kidney function, and to identify biomarkers of endothelial function, metabolomic profiles and clinical characteristics for the worsening of kidney function and for a rapid decline in kidney function.
"Funding Source - FDA OOPD"
Read the detailed description
Sickle cell disease is a severe monogenic disorder which affects approximately 80,000 patients in the US. It is characterized by a vasculopathy with involvement of multiple organs and resulting in complications such as ischemic stroke, pulmonary hypertension, autosplenectomy, priapism, as well as chronic kidney disease (CKD). Despite the high prevalence of CKD and its known association with increased mortality, the natural history of CKD and the factors associated with changes in kidney function in patients with SCD remain incompletely defined. Furthermore, the available treatment options for albuminuria, an early manifestation of CKD, in patients with SCD are limited. In fact, no controlled studies have confirmed the long-term efficacy of angiotensin-converting enzyme (ACE) inhibitors, the current "standard of care." There is increasing evidence for a contribution of endothelial dysfunction to the pathophysiology of albuminuria in SCD. The association of biomarkers of endothelial function with albuminuria provides opportunities, not only to assess the effect of therapies which improve endothelial function, but also to evaluate the predictive value of these biomarkers for a decline in kidney function. The long-range goal is to develop a model to identify patients at particularly high risk for a decline in kidney function.
In this study, the investigators will evaluate rate of change in kidney function (decline in estimated glomerular filtration rates and increase in albuminuria) and identify biomarkers of endothelial function, metabolomic profiles and clinical characteristics for the worsening of kidney function and for a rapid decline in kidney function. At the conclusion of this proposed work, the investigators will have an improved understanding of the natural history of CKD in sickle cell anemia. With the limited available therapies for the treatment of albuminuria in SCD and the paucity of data on the long-term efficacy of available pharmacotherapies, identification of biomarkers for the progression of CKD will facilitate the development of treatments which may be more effective than the current "standard of care."
- Conditions
- Sickle Cell Disease, Kidney Failure, Chronic
- Medical subject headings
- Anemia, Sickle Cell, Kidney Failure, Chronic
What is being measured
The primary outcome is the main question the study is designed to answer.
Age- and sex-adjusted rate of change, over 36 - 48 months, in estimated glomerular filtration rate in patients with sickle cell anemia
Estimated glomerular filtration rate will be ascertained using the CKD EPI equation
Measured: 36-48 months
Age- and sex-adjusted rate of change, over 36 - 48 months, in albuminuria in patients with sickle cell anemia
Evaluate the rate of change in albuminuria by spot urine measurements of albumin-creatinine ratio during designated study visits
Measured: 36-48 months
Cross-sectional association of biomarkers of endothelial function with kidney function (estimated glomerular filtration rate and albuminuria) in patients with sickle cell anemia
Plasma levels of ET-1, VEGF and soluble VCAM-1 from samples obtained at designated study visits will serve as measures of endothelial function
Measured: 36-48 months
Cross-sectional association of urine and plasma metabolomics profiles with kidney function (estimated glomerular filtration rates and albuminuria) in patients with sickle cell anemia
Untargeted metabolic profiling of plasma and urine will be performed using high-resonance nuclear magnetic resonance spectrometry. Plasma and urine analytes which are significantly associated with estimated glomerular filtration rate and albumin-creatinine ratio will be ascertained.
Measured: 36-48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2017
- Study start17 Nov 2017
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kenneth Ataga MD
- Sponsor type
- University, hospital or other
- Collaborators
- Ohio State University, University of North Carolina
- Responsible party
- Sponsor-investigator, Kenneth Ataga MD, University of Tennessee
- Investigators
- Kenneth Ataga, MD, Principal investigator, UTHSC Center for Sickle Cell Disease
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03277547
- Sponsor's protocol ID
- 17-0936
- Other IDs
- 1R01FD006030-01
- Status last verified
- Jan 2025
- First submitted
- 1 Sep 2017
- Last updated
- 27 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ataga KI, Brittain JE, Moore D, Jones SK, Hulkower B, Strayhorn D, Adam S, Redding-Lallinger R, Nachman P, Orringer EP. Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease: potential role of soluble fms-like tyrosine kinase-1. Eur J Haematol. 2010 Sep;85(3):257-63. doi: 10.1111/j.1600-0609.2010.01471.x. Epub 2010 Jun 3.
PubMed 20491879Ataga KI, Derebail VK, Archer DR. The glomerulopathy of sickle cell disease. Am J Hematol. 2014 Sep;89(9):907-14. doi: 10.1002/ajh.23762. Epub 2014 Jun 19.
PubMed 24840607Ataga KI, Brittain JE, Jones SK, May R, Delaney J, Strayhorn D, Desai P, Redding-Lallinger R, Key NS, Orringer EP. Association of soluble fms-like tyrosine kinase-1 with pulmonary hypertension and haemolysis in sickle cell disease. Br J Haematol. 2011 Feb;152(4):485-91. doi: 10.1111/j.1365-2141.2010.08410.x. Epub 2011 Jan 11.
PubMed 21223248Zhou LY, Derebail VK, Desai PC, Elsherif L, Patillo KL, McCune P, Wichlan D, Landes K, Ogu UO, Nelson M, Loehr LR, Cronin RM, Tang Y, Cai J, Ataga KI. Persistent albuminuria and chronic kidney disease in adults with sickle cell anaemia: Results from a multicenter natural history study. Br J Haematol. 2024 Sep;205(3):1159-1169. doi: 10.1111/bjh.19636. Epub 2024 Jul 8.
PubMed 38978309
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Association of Biomarkers of Endothelial Function With Prospective Changes in Kidney Function in Sickle Cell Anemia
- ClinicalTrials.gov ID
- NCT03277547
- Acronym / sponsor ID
- 17-0936
- Conditions
- Sickle Cell Disease, Kidney Failure, Chronic
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Kenneth Ataga MDUniversity, hospital or other
- Collaborators
- Ohio State University, University of North Carolina
- Study start
- 17 Nov 2017 (actual)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 11 Sep 2017 (actual)
- 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.
This is a prospective clinical cohort study that involves a baseline study visit followed by up to 3 annual follow-up study visits for a total follow-up of 36-48 months to evaluate the age- and sex-adjusted rate of change in kidney function, and to identify biomarkers of endothelial function, metabolomic profiles and clinical characteristics for the worsening of kidney function and for a rapid decline in kidney function.
"Funding Source - FDA OOPD"
Detailed description
Sickle cell disease is a severe monogenic disorder which affects approximately 80,000 patients in the US. It is characterized by a vasculopathy with involvement of multiple organs and resulting in complications such as ischemic stroke, pulmonary hypertension, autosplenectomy, priapism, as well as chronic kidney disease (CKD). Despite the high prevalence of CKD and its known association with increased mortality, the natural history of CKD and the factors associated with changes in kidney function in patients with SCD remain incompletely defined. Furthermore, the available treatment options for albuminuria, an early manifestation of CKD, in patients with SCD are limited. In fact, no controlled studies have confirmed the long-term efficacy of angiotensin-converting enzyme (ACE) inhibitors, the current "standard of care." There is increasing evidence for a contribution of endothelial dysfunction to the pathophysiology of albuminuria in SCD. The association of biomarkers of endothelial function with albuminuria provides opportunities, not only to assess the effect of therapies which improve endothelial function, but also to evaluate the predictive value of these biomarkers for a decline in kidney function. The long-range goal is to develop a model to identify patients at particularly high risk for a decline in kidney function.
In this study, the investigators will evaluate rate of change in kidney function (decline in estimated glomerular filtration rates and increase in albuminuria) and identify biomarkers of endothelial function, metabolomic profiles and clinical characteristics for the worsening of kidney function and for a rapid decline in kidney function. At the conclusion of this proposed work, the investigators will have an improved understanding of the natural history of CKD in sickle cell anemia. With the limited available therapies for the treatment of albuminuria in SCD and the paucity of data on the long-term efficacy of available pharmacotherapies, identification of biomarkers for the progression of CKD will facilitate the development of treatments which may be more effective than the current "standard of care."
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with HbSS or HbSB0 thalassemia between the ages of 18 and 65 years who meet the eligibility criteria and provide consent to participate in the study
Key inclusion criteria (4 listed)
- age of 18 to 65 years;
- confirmed diagnosis of sickle cell anemia (HbSS and SB0 thalassemia);
- non-crisis, "steady state" with no severe pain episodes requiring medical contact during the preceding 4 weeks;
- ability to understand the requirements of the study and be willing to give informed consent.
Key exclusion criteria (9 listed)
- bone marrow transplantation;
- history of long-standing diabetes mellitus with suspicion for diabetic nephropathy as determined by a nephrologist;
- known diagnosis of hepatitis B or C infection (patients will not be screened specifically for this during the study);
- known HIV positive (patients will not be screened specifically for this);
- history of cancer, except non-melanoma skin cancer;
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
Age- and sex-adjusted rate of change, over 36 - 48 months, in estimated glomerular filtration rate in patients with sickle cell anemia
Time frame: 36-48 months
Estimated glomerular filtration rate will be ascertained using the CKD EPI equation
Age- and sex-adjusted rate of change, over 36 - 48 months, in albuminuria in patients with sickle cell anemia
Time frame: 36-48 months
Evaluate the rate of change in albuminuria by spot urine measurements of albumin-creatinine ratio during designated study visits
Cross-sectional association of biomarkers of endothelial function with kidney function (estimated glomerular filtration rate and albuminuria) in patients with sickle cell anemia
Time frame: 36-48 months
Plasma levels of ET-1, VEGF and soluble VCAM-1 from samples obtained at designated study visits will serve as measures of endothelial function
Cross-sectional association of urine and plasma metabolomics profiles with kidney function (estimated glomerular filtration rates and albuminuria) in patients with sickle cell anemia
Time frame: 36-48 months
Untargeted metabolic profiling of plasma and urine will be performed using high-resonance nuclear magnetic resonance spectrometry. Plasma and urine analytes which are significantly associated with estimated glomerular filtration rate and albumin-creatinine ratio will be ascertained.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2025.
- Background: PubMed 20491879Ataga KI, Brittain JE, Moore D, Jones SK, Hulkower B, Strayhorn D, Adam S, Redding-Lallinger R, Nachman P, Orringer EP. Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease: potential role of soluble fms-like tyrosine kinase-1. Eur J Haematol. 2010 Sep;85(3):257-63. doi: 10.1111/j.1600-0609.2010.01471.x. Epub 2010 Jun 3.
- Background: PubMed 24840607Ataga KI, Derebail VK, Archer DR. The glomerulopathy of sickle cell disease. Am J Hematol. 2014 Sep;89(9):907-14. doi: 10.1002/ajh.23762. Epub 2014 Jun 19.
- Background: PubMed 21223248Ataga KI, Brittain JE, Jones SK, May R, Delaney J, Strayhorn D, Desai P, Redding-Lallinger R, Key NS, Orringer EP. Association of soluble fms-like tyrosine kinase-1 with pulmonary hypertension and haemolysis in sickle cell disease. Br J Haematol. 2011 Feb;152(4):485-91. doi: 10.1111/j.1365-2141.2010.08410.x. Epub 2011 Jan 11.
- Derived from this study: PubMed 38978309Zhou LY, Derebail VK, Desai PC, Elsherif L, Patillo KL, McCune P, Wichlan D, Landes K, Ogu UO, Nelson M, Loehr LR, Cronin RM, Tang Y, Cai J, Ataga KI. Persistent albuminuria and chronic kidney disease in adults with sickle cell anaemia: Results from a multicenter natural history study. Br J Haematol. 2024 Sep;205(3):1159-1169. doi: 10.1111/bjh.19636. Epub 2024 Jul 8.
- 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.
Kenneth Ataga, MD principal investigator
UTHSC Center for Sickle Cell Disease
3 sites 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 Kidney Failure, Chronic, run by Kenneth Ataga MD at 3 sites 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 4 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 27 Jan 2025. 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. 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?
This study is still under way. Results are not available in the source record yet.
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?
Age- and sex-adjusted rate of change, over 36 - 48 months, in estimated glomerular filtration rate in patients with sickle cell anemia (time frame: 36-48 months). The study lists 4 primary outcomes in all. 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 NCT03277547, which also lists 4 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 27 Jan 2025.