Effect of Phosphate Binders on Markers of Vascular Health in Chronic Kidney Disease Stages 3 and 4

Study Overview
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Brief Summary
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Chronic kidney disease (CKD) patients often have high levels of a substance called fibroblast growth factor-23 (FGF-23), a phosphorus excreting hormone, which has been related to heart disease. As kidney function declines, less phosphorus is removed by the kidneys and as a result phosphorus accumulates in the blood. In response to elevated phosphorus levels, more FGF-23 is released to help facilitate the excretion of extra phosphorus into the urine. In addition to effects on FGF-23, increased phosphorus levels can lead to calcification (hardening) of the blood vessels in the CKD population. Phosphate binding medicines are used in CKD patients to lower the amount of phosphorus absorbed by the stomach and intestines after eating meals and snacks. In patients with CKD, studies have shown that phosphate binders can lower FGF-23 levels in the blood. Lowering FGF-23 levels in CKD patients may also lower substances in the blood that cause calcification of blood vessels in the CKD population. This study is being done to determine if using phosphate binders, either sevelamer carbonate or calcium acetate, in the earlier stages kidney disease (before dialysis) can decrease FGF-23 and biomarkers (substances in the blood) associated with hardening of the blood vessels and heart disease.

Official Title
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A Randomized Study on the Effects of Sevelamer Carbonate Versus Calcium Acetate on Biomarkers of Vascular Calcification, Inflammation, and Endothelial Dysfunction in Chronic Kidney Disease Stages 3 and 4

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Sevelamer carbonate
* Drug: Calcium acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥ 18 years of age at start of screening CKD stage 3 or 4 defined by an eGFR 15 - 60 mL/min/1.73m2 Not expected to start dialysis for 8 months Serum intact PTH < 500 pg/mL during screening period On a stable ACE inhibitor/ARB regimen for 30 days prior to screening Exclusion Criteria: History of any of the following diseases: congestive heart failure, MI within the last 6 months, cerebrovascular accident, significant valvular disease, malignancy Currently receiving erythropoiesis stimulating agent or IV iron therapy History of inflammatory/autoimmune disease History of polycystic kidney disease HIV positive or AIDS Pregnant or breastfeeding Receiving activated Vitamin D analogs, nutritional vitamin D agents > 2,000 IU/day, or calcimimetics with in the last 3 months Significant GI disorder Proteinuria >3.5 g/24 hours

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sevelamer carbonate<br>1,600 mg (2 x 800 mg) three times daily with meals for a total of 12 weeks | Drug: Sevelamer carbonate<br>* Sevelamer carbonate 1,600 mg three times daily with meals<br>* Other names: Renvela;|
| Active Comparator: Calcium acetate<br>1,334 mg (2 x 667 mg) three times daily with meals for a total of 12 weeks | Drug: Calcium acetate<br>* Calcium acetate 1,334 mg three times daily with meals for 12 weeks<br>* Other names: Phoslo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure will be the change in FGF-23 concentrations |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in vascular calcification biomarker levels |  | 12 weeks | 
| Change in endothelial dysfunction biomarker levels. |  | 12 Weeks | 
| Change in inflammatory biomarker levels |  | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic kidney disease, Phosphate binder, Sevelamer carbonate, Calcium acetate, Vascular calcification, Endothelial Dysfunction