Effect of Sevelamer on Glucose Tolerance and Insulin Sensitivity in Patients With Chronic Renal Failure (CKD)

Study Overview
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Brief Summary
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The purpose of this study is to perform a randomized, controlled clinical trial to investigate if the phosphate binder sevelamer can improve insulin resistance and glucose handling in patients receiving maintenance hemodialysis.

Official Title
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Study of the Effect of Treatment With Sevelamer on Glucose Tolerance and Insulin Sensitivity in Patients With Chronic Renal Failure

Conditions
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Kidney Failure, Chronic, End-Stage Renal Disease, Insulin Resistance, Hyperphosphatemia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients 18-80 years of age with chronic renal failure treated with maintenance HD for >3 months. Exclusion Criteria: Diabetes mellitus Treatment with sevelamer within 3 months prior to enrollment Acute, clinically significant inflammation within 1 month prior to enrollment Pregnancy or breast-feeding Clinically significant obstipation or bowel obstruction Discontinuation of previous sevelamer treatment because of side effects Expected time in HD < 1 year Unwillingness to undergo the investigations and follow-up required in the the protocol Patients who have received any investigational drug within 1 month prior to enrolment Participation in another study, which may interfere with the present study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Sevelamer intervention | Drug: Sevelamer<br>* sevelamer tablets, 800 mg (Renagel(r), Genzyme Inc). The initial daily dose of sevelamer will be 2400 mg (800 mg x 3). After the first week of treatment the dose will be increased to 4800 mg. If treatment with sevelamer is well tolerated and if a phosphate concentration of <1.8 mmol/l is not obtained, the dose may be increased further. The maximum daily dose of sevelamer will be 9600 mg. If a patient experiences side effects, the dose of sevelamer will be reduced to the highest acceptable dose, and, if a phosphate concentration of <1.8 mmol/l is not obtained, the treatment will be supplemented with calcium carbonate in a dose tolerated by the patient.<br>* Other names: Renagel;|
| Active Comparator: 2<br>Calcium carbonate | Drug: Calcium carbonate<br>* Calcium carbonate tablets, 250 mg (Kalcidon, Abigo AB). Calcium carbonate will be prescribed at the dose given prior to the washout period. The dose will be adjusted weekly to obtain a serum phosphate concentration <1.8 mmol/l.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin sensitivity and/or glucose tolerance from baseline to the end of the study, as obtained by ISIOGTT. |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to the end of the trial in surrogate markers of phosphate balance (PTH, s-urea, s-creatinine, ionized Ca, phosphate). |  | Week 12 | 
| Change from baseline to end of the study in markers of lipid homeostasis (total cholesterol, LDL, HDL, ApoA, ApoB, TG, free fatty acids) |  | Week 12 | 
| Change from baseline to the end of the study in circulating inflammatory cytokines (hsCRP, TNF, fibrinogen, PAI, fetuin) |  | Week 12 | 
| Number of adverse events directly attributable to sevelamer or calciumcarbonate treatments. |  | Weekly until end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic kidney disease, End-stage renal disease, phosphate binder, insulin resistance, glucose intolerance, sevelamer