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

Sponsor

Karolinska Institutet (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00837655

Collaborator

Göteborg University (Other)

Enrollment

Locations

Arms

28.9

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Failure, Chronic End-Stage Renal Disease Insulin Resistance Hyperphosphatemia	Drug: Sevelamer Drug: Calcium carbonate	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2009

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Sevelamer intervention	Drug: Sevelamer 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. Other Names: Renagel
Active Comparator: 2 Calcium carbonate	Drug: Calcium 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.

Arm

Intervention/Treatment

Experimental: 1

Sevelamer intervention

Drug: Sevelamer

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.

Other Names:

Renagel

Active Comparator: 2

Calcium carbonate

Drug: Calcium 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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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