Effect of an L-carnitine-containing Peritoneal Dialysis (PD) Solution on Insulin Sensitivity in 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 measured by a hyperinsulinemic euglycemic clamp.

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, Insulin Resistance

Intervention / Treatment
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* Drug: PD solution containing glucose
* Drug: PD solution containing glucose and 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 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 (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 6 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 Be in treatment with androgens Have Diabetes Mellitus (as defined by the American Diabetes Society, objectively documented by a fasting plasma glucose and HbA1c determinations) 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 NCS 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, particularly if patient's life expectancy is less than 1 year 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: Glucose solution<br> | Drug: PD solution containing glucose<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 120 days.<br>* Other names: Dianeal (Baxter);|
| Experimental: Glucose and L-carnitine solution<br> | Drug: PD solution containing glucose and 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 120 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 euglycemic hyperinsulinemic clamp |  | time 0, 4 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 |  | -2 weeks, time 0, 1 month, 2 months, 3 months, 4 months | 
| To assess the efficacy of L-Carnitine containing PD solution on hematological parameters (hemoglobin and EPO requirements) |  | -2 weeks, time 0, 2 months, 4 months | 

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