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Active, not recruitingNCT03277547Updated Jan 27, 2025

Kidney Function in Sickle Cell Anemia

An observational study in Sickle Cell Disease and Kidney Failure, Chronic, sponsored by Kenneth Ataga MD. Active, not recruiting at 3 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-01-27.

Sponsored by Kenneth Ataga MD · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
300
Ages
18 Years to 65 Years
Sex
All
01

Study 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"

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."

02

Conditions studied

  • Sickle Cell Disease
  • Kidney Failure, Chronic
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No
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

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

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.
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
300 participants (estimated)
Patient registry
No
Biospecimen retention
Samples without dna
05

What researchers measure

Primary outcomes

  1. 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

    Time frame: 36-48 months

  2. 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

    Time frame: 36-48 months

  3. 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

    Time frame: 36-48 months

  4. 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.

    Time frame: 36-48 months

06

Study locations

3 sites
  • University of North Carolina-Chapel Hill
    Chapel Hill, North Carolina 27599, United States
  • Ohio State Adult Sickle Cell Program
    Columbus, Ohio 43210, United States
  • UTHSC Center for Sickle Cell Disease
    Memphis, Tennessee 38163, United States
07

References and documents

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 20491879 ↗
  • 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. PubMed 24840607 ↗
  • 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. PubMed 21223248 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03277547
Lead sponsor
Kenneth Ataga MD
Collaborators
Ohio State University, University of North Carolina
Responsible party
Kenneth Ataga MD (Professor, University of Tennessee) — Sponsor-investigator
First posted
Sep 11, 2017
Start date
Nov 17, 2017
Primary completion
Jun 1, 2025 (estimated)
Completion
Dec 1, 2025 (estimated)
Last update
Jan 27, 2025

Study contacts

Kenneth Ataga, MD
principal investigator · UTHSC Center for Sickle Cell Disease

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.

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