Dianeal, Extraneal, Nutrineal (D-E-N) Versus Dianeal Only in Diabetic Continuous Ambulatory Peritoneal Dialysis (CAPD) Patients

Study Overview
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Brief Summary
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Primary Objective: To demonstrate that use of glucose sparing prescriptions, Dianeal, Extraneal, Nutrineal (D-E-N) versus Dianeal only, in diabetic (Type 1 and Type 2) Continuous Ambulatory Peritoneal Dialysis (CAPD) patients leads to improved metabolic control as measured by the magnitude of change from the baseline value in the HbA1c levels. Secondary Objectives: To demonstrate that use of glucose-sparing Peritoneal Dialysis solutions (D-E-N versus Dianeal only) in diabetic (Type 1 and Type 2) CAPD patients leads to lower glycemic-control medication requirements, decreased incidence of severe hypoglycemic events requiring medical intervention, improved metabolic control, nutritional status, and Quality of Life.

Official Title
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Multi-center, Prospective, Randomized Trial to Demonstrate Improved Metabolic Control of Dianeal, Extraneal, Nutrineal (D-E-N) Versus Dianeal Only in the Treatment of Diabetic CAPD Patients

Conditions
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End Stage Renal Disease (ESRD), Diabetes, CAPD

Intervention / Treatment
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* Drug: Dianeal
* Drug: Dianeal, Extraneal, Nutrineal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female patients 18 years of age or older Diagnosis of ESRD [Glomerular Filtration Rate (GFR) ≤ 15 mL/min] CAPD using only Dianeal, at least 1 exchange of 2.5% or 4.25% dextrose/day, no prescribed dry time Diabetes Mellitus (Type 1 and 2) HbA1c > 6.0% but ≤ 12.0% Blood hemoglobin ≥ 8.0 g/dL, but ≤ 13.0 g/dL Total Kt/V ≥ 1.7 Exclusion Criteria: Blood Urea Nitrogen (BUN) > 95 mg/dL Exposure to Extraneal within 60 days of Screening Mean Arterial Pressure (MAP) ≥ 125 mm Hg, or volume depleted (MAP < 77mm Hg) at Screening Peritonitis, exit-site or tunnel infection treated with antibiotics within last 30 days Cardiovascular event within the last 30 days Ongoing clinically significant congestive heart failure [New York Heart Association (NYHA) class III or IV] Allergy to starch-based polymers, glycogen storage disease or isomaltose/maltose intolerance Receiving rosiglitazone maleate

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: Non-glucose Sparing<br>Dianeal only | Drug: Dianeal<br>* Dianeal 1.5% dextrose, 2.5% dextrose, 4.25% dextrose<br>|
| Experimental: Glucose Sparing<br>Dianeal, Extraneal, Nutrineal | Drug: Dianeal, Extraneal, Nutrineal<br>* Dianeal 1.5% dextrose, 2.5% dextrose, 4.25% dextrose, Nutrineal 1.1% Amino Acids, Extraneal 7.5% Icodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From the Baseline Value in HbA1c at Month 3 and 6 | HbA1c is a specific glycohemoglobin, and adduct of glucose attached to the beta-chain terminal valine residue. Measured using a Tina-quant immunological assay suitable for samples from end stage renal disease (ESRD) patients and with icodextrin metabolites or equivalent. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycemic Control Medication Usage at Month 3 and 6 | This data used diabetic prescription drug information from insulin and oral glycemic control concomitant medications reported. Glycemic control medications classes allowed were limited to insulin, sulfonylureas, and thiazolidinediones. Subjects were provided with a paper diary on which they recorded doses of all glycemic control medications taken for 1 day prior to the Screening visit and for 8 days prior to the study visits at Month 3 and Month 6. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Number of Severe Hypoglycemic Event Requiring Medical Intervention | Severe hypoglycemia is defined by DCCT (Diabetes Control and Complications Trial) as any episode requiring external assistance to aid recovery or resulted in seizures or coma and included, as part of the definition, that the subject's blood glucose concentration had to have been documented as < 50mg/dL (<2.8mmol/L) for hypoglycemia, and/or the clinical manifestations had to have been reversed with oral carbohydrate, intramuscular glucagon, or intravenous glucose. Descriptive statistics were done, no inferential statistical analyses were performed. | Baseline through Month 6 (End of Study) | 
| Change From Baseline of Metabolic Control Determined by Lipid Profile and Triglycerides at Month 3 and 6 | Values for Total Cholesterol (TC), Low Density Lipoprotein Cholesterol (LDLC), High Density Lipoprotein Cholesterol (HDLC), Very Low Density Lipoprotein (VLDL), and Triglycerides are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline of Metabolic Control Determined by Lipoproteins at Month 3 and 6 | Values for Lipoprotein A (Lp(a)), Apolipoprotein A1 (Apo A1), and Apolipoprotein B (Apo B) are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline of Metabolic Control Determined by Insulin Action of Insulin and C-peptide at Month 3 and 6 | Values for Insulin and C-peptide are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline of Metabolic Control Determined by Insulin Action of Pro-Insulin at Month 3 and 6 | Values for Pro-Insulin are provided. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Number of Participants by Change From Baseline Score in Subjective Global Assessment (SGA) Class at Month 6 | Nutritional Status by SGA include the following: (a) Weight change over 6 months, (b) dietary history of food intake over the previous 24-hour period with a determination by the subject as to whether this was a typical or atypical diet for the subject, (c) significant and sustained gastrointestinal distress, (d) functional status, (e) metabolic stress including frequent infections, fever, peritonitis, uncontrolled diabetes and active inflammatory bowel disease. The SGA used a 7-point scale, where a decrease score in the change from baseline shows signs of increased malnourishment, and an increased score (e.g., +2) is improved nourishment. Scale: 6 - 7 = very mild risk to well-nourished; 3 - 5 = no clear sign of normal status or severe malnutrition; 1 - 2 = severely malnourished. | Baseline and Month 6 (End of Study) | 
| Change From Baseline of Nutritional Status Determined by Albumin and Total Protein (Labs) at Month 3 and 6 | Values for Albumin and Total Protein are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline of Nutritional Status Determined by PNA and nPNA (Labs) at Month 3 and 6 | Values for Protein Nitrogen Appearance (PNA) and normalized protein nitrogen appearance (nPRNA) are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline of Nutritional Status Determined by Pre-albumin (Labs) at Month 3 and 6 | Values for Pre-albumin are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline of Nutritional Status Determined by Drained Body Weight at Month 3 and 6 | Values for Drained Body Weight are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline of Nutritional Status Determined by Body Mass Index (BMI) at Month 3 and 6 | Values for BMI are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline of Nutritional Status Determined by Waist Circumference at Month 6 | Values for Waist Circumference are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 6 (End of Study) | 
| Change From Baseline of Nutritional Status Determined by Protein and Calories at Month 3 and 6 | Values for Protein and Calories are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline in QOL Based pm the EQ 5D Questionnaire Index at Month 3 and 6 | European Quality of Life, 5 Dimensions (EQ-5D) generates a single index score based on a descriptive system that defines health in terms of 5 dimensions, consisting of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The possible range for each dimension is 1 to 3, where 1=no problems, 2=moderate problems, 3=extreme problems. Higher score implies more problems (worsening). According to this classification, 243 potential health states are defined Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline in QOL Based on the EQ 5D Quest Health Status at Month 3 and 6 | Visual analogue scale to generate a self-perceived rating of health status. Visual analogue scale is the second part of the questionnaire, asking to mark health status on the day of the interview on a 20 cm vertical scale with end points of 0 and 100. There are notes at the both ends of the scale that the bottom rate (0) corresponds to  the worst health you can imagine, and the highest rate (100) corresponds to the best health you can imagine. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline in QOL Based on the Diabetes Symptom Checklist (DSC) at Month 3 and 6 | The Diabetes Symptoms Checklist was designed to assess the presence and perceived burden of diabetes-related symptoms. Respondents were to consider troublesomeness of 34 symptoms on a 5-point scale ranging from 5=extremely to 1=not at all. For symptoms/side-effects not experienced, the item was scored as 0. Symptoms were grouped into the following subscales: psychological fatigue, psychological cognitive, neurology pain, neurology sensory, cardiology, ophthalmology, hypoglycemia, hyperglycemia. Subscale scores were calculated as the sum of the given subscale divided by the total number of items in the scale. Total score was computed from the sum of the 8 subscales and ranged from 0 to 40. Higher scores indicate greater symptom burden. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 3, Month 6 (End of Study) | 
| Change From Baseline of MRI Body Composition at Month 6 | Values for Abdominal Subcutaneous Fat Volume and Abdominal Visceral Fat Volume are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 6 (End of Study) | 
| Change From Baseline of Left Ventricular (LV) End Diastolic and Systolic Volume as Determined by MRI at Month 6 | Values for Left Ventricular (LV) End Diastolic and Systolic Volume are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 6 (End of Study) | 
| Change From Baseline of Left Ventricular (LV) Mass Without and With Pap Muscles as Determined by MRI at Month 6 | Values for Left Ventricular (LV) Mass Without and With Pap Muscles are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 6 (End of Study) | 
| Change From Baseline of Left Ventricular (LV) Ejection Fraction as Determined by MRI at Month 6 | Values for Left Ventricular (LV) Ejection Fraction are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0. | Baseline, Month 6 (End of Study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ESRD, Diabetes, CAPD