Effect of an L-Carnitine-Containing Peritoneal Dialysis (PD) Solution on Insulin Sensitivity in Diabetic Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD)

Study Overview
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Brief Summary
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The current study is initiated in order to assess the impact of a PD solution containing L-carnitine on insulin sensitivity evaluated by measuring insulin requirement.

Official Title
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Phase 2 Study of the Effect of a Peritoneal Dialysis Solution Containing Glucose (1.5%) and L-Carnitine (0.1%) on Insulin Sensitivity in Patients on Continuous Ambulatory Peritoneal Dialysis

Conditions
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End Stage Renal Disease, Diabetes

Intervention / Treatment
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* Drug: PD Solution
* Drug: PD solution containing L-carnitine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Have a diagnosis of ESRD and have been on Continuous Ambulatory Peritoneal Dialysis (CAPD) for at least 3 months Have Type 2 Diabetes, diagnosed according to American Diabetes Association (fasting glucose ≥126 mg/dl and 2 h glucose at OGTT ≥200 mg/dl), and treated with multiple daily insulin injection or with HbA1c > 8.5% (No oral antidiabetic) Be in a stable clinical condition during the four weeks immediately prior to Screening Period as demonstrated by medical history, physical examination and laboratory testing Have a blood hemoglobin concentration above 8,5 g/100ml (data will be verified with Investigators) Have not experienced peritonitis episodes in the last 3 months Be treated with Extraneal (nocturnal exchange bag solution) for at least 1 month Be treated with 3 diurnal exchange bag solutions (solution bags with 1.5% or 2.5% glucose) and one nocturnal exchange bag solution (Extraneal) Have Kt/V urea measurement > 1.7 per week in a previous test performed within 3 months that should be confirmed at Baseline Visit Have a minimum weekly creatinine clearance of 45 litres in a previous test performed within 6 months that should be confirmed at Baseline Visit Have a D/P Creatinine ratio at Peritoneal Equilibration Test (PET) between 0.50 and 0.81 in a previous test performed within 6 months that should be confirmed at Baseline Visit Have a D/P Glucose ratio at Peritoneal Equilibration Test (PET) between 0.26 and 0.49 in a previous test performed within 6 months that should be confirmed at Baseline Visit Be treated by the participating clinical Investigator for a period of at least three months Have understood and signed the Informed Consent Form. Exclusion Criteria: Have a history of drug or alcohol abuse in the six months prior to entering the protocol Type 2 Diabetic patients under oral antidiabetic treatment with HbA1C < 8.5% Be in treatment with androgens Have clinically significant abnormal liver function test (SGOT, SGPT, and gamma-GT > 2 times the upper normal limit) Have acute infectious conditions (i.e.: pulmonary infection, acute hepatitis, high or low urinary tract infections, renal parenchymal infection, pericarditis, etc) Have a history of congestive heart failure and clinically significant arrhythmia Have an history of epilepsy or any CNS disease Have malignancy within the past 5 years, including lymphoproliferative disorders Have any medical condition that, in the judgment of the Investigator, would jeopardize the patient's safety following exposure to study drug Have a history of L-Carnitine therapy or use in the month prior to entering the protocol Have used any investigational drug in the 3 months prior to entering the protocol Be in pregnancy, lactation, fertility age without protection against pregnancy by adequate contraceptive means

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: A<br> | Drug: PD Solution<br>* Instillation of PD solutions containing Glucose (1.5 or 2.5%, w/v) for the diurnal exchanges, and 1 PD solution containing icodextrin (7.5 w/v) for nocturnal exchange. PD solutions are instilled for 180 days.<br>|
| Experimental: B<br> | Drug: PD solution containing L-carnitine<br>* Instillation of PD solutions containing Glucose (1.5 or 2.5%, w/v) and L-carnitine (0.1%, w/v) for the diurnal exchanges, and 1 PD solution containing icodextrin (7.5 w/v) for nocturnal exchanges. PD solutions are instilled for 180 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of L-Carnitine containing PD solution on insulin sensitivity evaluated by measuring insulin requirement |  | time 0, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of L-Carnitine containing PD solution on plasma lipids and lipoprotein profile |  | 4 weeks, time 0, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months | 
| To assess the efficacy of L-Carnitine containing PD solution on hematological parameters (hemoglobin and EPO requirements) |  | 2 weeks, time 0, 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peritoneal dialysis, L-carnitine, Diabetes, Glucose homeostasis, Dyslipidemia