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

NCT00837655 | Withdrawn DMC

• 1 other identifier: SIR_CT_CLINTEC_01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Chronic kidney disease; End-stage renal disease; phosphate binder; insulin resistance; glucose intolerance; sevelamer

Outcome Measures

Primary Outcomes (1)

• Change in insulin sensitivity and/or glucose tolerance from baseline to the end of the study, as obtained by ISIOGTT.

  Week 12

Secondary Outcomes (4)

• 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

Study Arms (2)

1

EXPERIMENTAL

Sevelamer intervention

Drug: Sevelamer

2

ACTIVE COMPARATOR

Calcium carbonate

Drug: Calcium carbonate

Interventions

Sevelamer DRUG

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.

Also known as: Renagel

1

Calcium carbonate DRUG

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.

2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18-80 years of age with chronic renal failure treated with maintenance HD for \>3 months.

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead
• Göteborg University: collaborator

Study Sites (2)

Sahlgrenska University Hospital

Gothenburg, Gothenburg, 413 45, Sweden

Location

Karolinska University Hospital

Stockholm, Stockholm County, 14186, Sweden

Location

Related Publications (1)

• Soonthornpun S, Setasuban W, Thamprasit A, Chayanunnukul W, Rattarasarn C, Geater A. Novel insulin sensitivity index derived from oral glucose tolerance test. J Clin Endocrinol Metab. 2003 Mar;88(3):1019-23. doi: 10.1210/jc.2002-021127.

  PMID: 12629079 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic; Insulin Resistance; Hyperphosphatemia; Renal Insufficiency, Chronic; Glucose Intolerance

Interventions

Sevelamer; Calcium Carbonate

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Phosphorus Metabolism Disorders; Hyperglycemia

Intervention Hierarchy (Ancestors)

Polyamines; Amines; Organic Chemicals; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals

Study Officials

• Anders Alvestrand, MD PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Jonas Axelsson, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 29, 2009
• First Posted: February 5, 2009
• Study Start: January 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: September 26, 2012

Record last verified: 2009-01

Locations

SE (2)