Sitagliptin in Renal Transplant Recipients

Study Overview
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Brief Summary
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The major cause of premature death in renal transplant recipients is cardiovascular disease. Sitagliptin stimulates insulin secretion and inhibits glucagon release, two central mechanisms in PTDM by interaction with a hormone system (incretins) that just recently it has become possible to modulate by drugs. Sitagliptin therefore is an interesting additional drug for the treatment of posttransplant diabetes mellitus in transplanted patients. The primary objective of the present study is to investigate the effect of sitagliptin on insulin secretion in renal transplant recipients. Secondary objectives are to study the effect on insulin sensitivity, fasting blood glucose, endothelial function, CsA/Tac blood concentrations.

Official Title
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The Effect of Sitagliptin Treatment on Glucose Metabolism and Endothelial Function in Renal Transplant Recipients - JANUVIA-08

Conditions
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Glucose Intolerance

Intervention / Treatment
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* Drug: sitagliptin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant recipient more than 1 year posttransplant with stable renal function (less than 20% deviation in serum creatinine the last 2 months) and stable prednisolone dose for the last 3 months before inclusion. Patients in need of (additional) oral anti-diabetic treatment: New onset diabetes patients with fasting plasma glucose 7-8 mmol/ l, and/or 2-hr plasma glucose 12-18 mmol/l after an oral glucose tolerance test (OGTT) Patients already on oral hypoglycemic therapy, but with HbA1c 8-11% 18 years of age. Male patient, or female patient without childbearing potential (surgically sterilized or postmenopausal) or, if female of childbearing potential, is not lactating, has a negative pregnancy test at screening and is willing to utilize an effective method of contraception throughout the study period and for 90 Days following discontinuation of the Study Drugs. Signed informed consent. Exclusion Criteria: Treatment with insulin Severe liver disease. Estimated GFR < 25 ml/min/1.73 m2. Skin disorders that may influence laser Doppler flowmetry investigations. Pregnant or nursing mothers.

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Patients will receive 4 weeks of treatment with sitagliptin once daily | Drug: sitagliptin<br>* Once daily sitagliptin. If GFR>50 ml/min/1.73m2: 100 mg/day. If GFR from 25 to 49 ml/min/1.3m2: 50 mg/day<br>* Other names: Januvia;|
| Placebo Comparator: B<br>No treatment for 4 weeks | Drug: placebo<br>* No active sitagliptin treatment for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretion |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity |  | 4 weeks | 
| Fasting blood glucose |  | 4 weeks | 
| Endothelial function |  | 4 weeks | 
| Cyclosporine/tacrolimus blood concentrations |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal transplantation, diabetes, glucose intolerance, impaired glucose tolerance