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Kidney Function in Sickle Cell Anemia

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ClinicalTrials.gov Identifier: NCT03277547
Recruitment Status : Recruiting
First Posted : September 11, 2017
Last Update Posted : January 9, 2018
Sponsor:
Collaborator:
Ohio State University
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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"


Condition or disease
Sickle Cell Disease Kidney Failure, Chronic

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
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Association of Biomarkers of Endothelial Function With Prospective Changes in Kidney Function in Sickle Cell Anemia
Actual Study Start Date : November 17, 2017
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  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 [ 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.


Biospecimen Retention:   Samples Without DNA
Plasma samples will be collected to measure biomarkers of endothelial function. Plasma and urine samples will be collected for measurement of metabolic profiles.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   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
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03277547


Locations
United States, North Carolina
University of North Carolina-Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Kenneth I Ataga, MD    919-843-7708    kenneth_ataga@med.unc.edu   
Contact: David Wichlan    919-966-6876    dwichlan@med.un.edu   
Principal Investigator: Kenneth I Ataga, MD         
Sub-Investigator: Vimal K Derebail, MD, MPH         
Sub-Investigator: Laila Elsherif, PhD         
Sub-Investigator: Jianwen Cai, PhD         
Sub-Investigator: Laura R Loehr, MD, PhD         
Sub-Investigator: Jeffrey MacDonald, PhD         
Sub-Investigator: Donglin Zeng, PhD         
Sub-Investigator: Payal C Desai, MD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Ohio State University
Investigators
Principal Investigator: Kenneth Ataga, MD University of North Carolina, Chapel Hill

Publications:
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03277547     History of Changes
Other Study ID Numbers: 17-0936
1R01FD006030-01 ( U.S. FDA Grant/Contract )
First Posted: September 11, 2017    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Anemia, Sickle Cell
Renal Insufficiency
Kidney Failure, Chronic
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic