Kidney Function in Sickle Cell Anemia

Sickle Cell Disease Clinical Trial

Official title:

The Association of Biomarkers of Endothelial Function With Prospective Changes in Kidney Function in Sickle Cell Anemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03277547
• Other study ID #: 17-0936
• Secondary ID: 1R01FD006030-01
• Status: Active, not recruiting
• Start date: November 17, 2017
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: University of Tennessee
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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 clinical characteristics for the worsening of kidney function and for a rapid decline in kidney function.

"Funding Source - FDA OOPD"

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."

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. age of 18 to 65 years;

2. confirmed diagnosis of sickle cell anemia (HbSS and SB0 thalassemia);

3. non-crisis, "steady state" with no severe pain episodes requiring medical contact during the preceding 4 weeks;

4. ability to understand the requirements of the study and be willing to give informed consent.

Exclusion Criteria:

1. bone marrow transplantation;

2. history of long-standing diabetes mellitus with suspicion for diabetic nephropathy as determined by a nephrologist;

3. known diagnosis of hepatitis B or C infection (patients will not be screened specifically for this during the study);

4. known HIV positive (patients will not be screened specifically for this);

5. history of cancer, except non-melanoma skin cancer;

6. pregnant or breastfeeding;

7. connective tissue disease such as SLE;

8. known glomerular disease unrelated to SCD;

9. patients with ESRD on chronic dialysis.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Kidney Failure, Chronic
• Renal Insufficiency
• Sickle Cell Disease

Locations

Country	Name	City	State
United States	University of North Carolina-Chapel Hill	Chapel Hill	North Carolina
United States	Ohio State Adult Sickle Cell Program	Columbus	Ohio
United States	UTHSC Center for Sickle Cell Disease	Memphis	Tennessee

Sponsors (3)

Lead Sponsor	Collaborator
Kenneth Ataga MD	Ohio State University, University of North Carolina

Country where clinical trial is conducted

United States, 

References & Publications (3)

Ataga 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. — View Citation

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. — View Citation

Ataga 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	36-48 months
Primary	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	36-48 months
Primary	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	36-48 months
Primary	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.	36-48 months