Kidney Failure, Chronic, End-Stage Renal Disease, Insulin Resistance, Hyperphosphatemia
Conditions
Keywords
Chronic kidney disease, End-stage renal disease, phosphate binder, insulin resistance, glucose intolerance, sevelamer
Brief summary
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.
Interventions
DRUGSevelamer
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.
DRUGCalcium carbonate
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.
Sponsors
Göteborg University
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
Sweden
Outcome results
None listed