A Prospective, Multicenter, Randomized, Open-label Study of 12 Week Duration to Evaluate the Effect of VILDagliptin Added to Insulin on Glycaemic Control in haemoDIALyzed Patients With Type 2 Diabetes: Probe Analysis of CGM

Study Overview
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Brief Summary
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Diabetes is a major concern for dialysis units, as it is now the most common cause of end-stage renal disease in France. In 2010 at initiation of dialysis treatment, more than one patient out of two had at least one cardiovascular disease and 40 % diabetes (94 % Type 2 diabetes) and especially in East part of France. Diabetic patients on dialysis have a high burden of morbidity and mortality, particularly from cardiovascular disease. Tight glycaemic and blood pressure control in diabetic patients has an important impact in reducing risk of progression nephropathy. Data are scarce on how diabetes should best be treated in dialysis patients. The evidence for improving glycaemic control in patients on dialysis having an impact on mortality or morbidity is sparse. Indeed, many factors make improving glycaemic control in patients on dialysis very challenging, including therapeutic difficulties with hypoglycaemic agents, monitoring difficulties, dialysis strategies that exacerbate hyperglycaemia or hypoglycaemia. Standard oral drugs therapy for hyperglycaemia (eg, metformin, sulfonylureas, ) are contraindicated in patients on dialysis. Thus insulin has been the mainstay of treatment. Newer therapies for hyperglycaemia, such as gliptins and glucagon-like peptide-1 analogues have become available, but until recently, renal failure has precluded their use. Newer gliptins, however, are now licensed for use in 'severe renal failure', although they have yet to be trialed in dialysis patients. The investigators study, using continuous glucose monitoring as a new tool for monitoring of therapy should provide information on vildagliptin in add on therapy to insulin in this population.

Official Title
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A Prospective, Multicenter, Randomized, Open-label Study of 12 Week Duration to Evaluate the Effect of VILDagliptin Added to Insulin on Glycaemic Control in haemoDIALyzed Patients With Type 2 Diabetes: Probe Analysis of CGM

Conditions
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Haemodialyzed, Type 2 Diabetes

Intervention / Treatment
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* Drug: Vildagliptin (Galvus)
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients treated by haemodialysis for more than 3 months with 1g/L glucose in dialysate fluid Patients treated by stable doses of insulin (any regimen) for Type 2 diabetes without any oral antidiabetic agent Age > 18 years TGO, TPO and lipase < 3x ULN effective means of contraception Non-inclusion Criteria: Blood transfusion in the 2 previous months Life expectancy less than 1 year Chronic inflammatory disease Steroid treatment > 5mg/day Cancer (evolutive or requiring chemotherapy or radiotherapy) with the exception of breast intraductal carcinoma operated Patient waiting for programmed surgery History of cardiovascular disease (stroke, coronary heart disease, hospitalization for heart failure) in the 4 previous months Patients suffering from stage 3 and 4 cardiac insufficiency Non-compliant patients History of pancreatitis History of angioedema Hypersensitivity to the active substance or to any of the excipients of Galvus® Pregnancy or breastfeeding

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin alone<br>Use the usual frequency and dose | Drug: Insulin<br>* Insulin<br>|
| Experimental: Insulin and Vildagliptin<br>vildagliptin 50 mg/day during 3 months | Drug: Vildagliptin (Galvus)<br>* Use Vildagliptin (50 mg/day) added to insulin during 3 months<br>Drug: Insulin<br>* Insulin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean glucose value of CGM [M] to be averaged from day 2 and day 3 of CGM |  | up to day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGM parameters at baseline and month 3 | glucose area under the curve (AUC) for glucose value higher than 7.7 mmol/l number of glucose values under 3.3 mmol/l hypoglycaemic events at baseline, month 3 number of minor hypoglycaemic events per month number of major hypoglycaemic events at month 3 number of nocturnal hypoglycaemic events per month variability glycemic index: MAGE, CV | Other CGM parameters at baseline and month 3 | 
| Number of hypoglycaemic events | hypoglycaemic events at baseline, month 3 number of minor hypoglycaemic events per month number of major hypoglycaemic events at month 3 number of nocturnal hypoglycaemic events per month | Hypoglycaemic events at baseline, month 3 | 
| Mean HbA1C and Glycated albumin |  | HbA1C and Glycated albuminat baseline and month 3 |