Kidney Function in Sickle Cell Anemia

• ClinicalTrials.gov Identifier: NCT03277547
• Recruitment Status: Active, not recruiting
• First Posted: September 11, 2017
• Last Update Posted: March 6, 2023
• Sponsor: Kenneth Ataga MD
• Collaborators: Ohio State University; University of North Carolina
• Information provided by (Responsible Party): Kenneth Ataga MD, University of Tennessee

Tracking Information

• First Submitted Date: September 1, 2017
• First Posted Date: September 11, 2017
• Last Update Posted Date: March 6, 2023
• Actual Study Start Date: November 17, 2017
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 7, 2017)

• 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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Kidney Function in Sickle Cell Anemia
• Official Title: The Association of Biomarkers of Endothelial Function With Prospective Changes in Kidney Function in Sickle Cell Anemia

Brief 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"

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 Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Plasma samples will be collected to measure biomarkers of endothelial function. Plasma and urine samples will be collected for measurement of metabolic profiles.

• Sampling Method: Non-Probability Sample
• 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

Condition

• Sickle Cell Disease
• Kidney Failure, Chronic

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: September 7, 2017): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03277547
• Other Study ID Numbers: 17-0936; 1R01FD006030-01 ( U.S. FDA Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Kenneth Ataga MD, University of Tennessee
• Original Responsible Party: University of North Carolina, Chapel Hill
• Current Study Sponsor: Kenneth Ataga MD
• Original Study Sponsor: University of North Carolina, Chapel Hill

Collaborators

• Ohio State University
• University of North Carolina

Investigators

• Principal Investigator: Kenneth Ataga, MD; UTHSC Center for Sickle Cell Disease

• PRS Account: University of Tennessee
• Verification Date: March 2023