Effect of an L-carnitine-containing Peritoneal Dialysis (PD) Solution on Insulin Sensitivity in Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD)

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

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.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; End Stage Renal Disease
• Intervention / Treatment: Drug: PD solution containing glucose; Drug: PD solution containing glucose and L-carnitine

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70124
    • Renal, Dialysis and Transplant Unit, University of Bari
  • Bari, Italy, 70124
    • Renal and Dialysis, Bari Policlinic Hospital
  • Chieti, Italy, 66100
    • Division of Nephrology, University of "G. d'Annunzio"
  • Desio, Italy, 20100
    • Nephrologyand Dialysis Unit, Desio Hospital
  • Giulianova, Italy, 64021
    • Nephrology and Dialysis Unit, "Maria SS dello Splendore" Hospital
  • Lanciano, Italy, 66034
    • Nephrology and Dialysis Unit, "Renzetti" Hospital
  • Milano, Italy, 20121
    • Division of Nephrology and Dialysis, Ospedale Policlinico Maggiore
  • Ortona, Italy, 66026
    • Nephrology and Dialysis Unit, "G. Bernabeo" Hospital
  • Sesto San Giovanni, Italy, 20099
    • Renal Unit, Policlinico MultiMedica
  • Sulmona, Italy, 67039
    • Nephrology and Dialysis Unit, "SS Annunziata" Hospital
  • Teramo, Italy, 64100
    • Division of Nephrology and Dialysis, "Mazzini" Hospital
  • Vasto, Italy, 66054
    • Nephrology and Dialysis Unit, "San Pio da Pietrelcina" Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years
2. Have a diagnosis of ESRD and have been on Continuous Ambulatory Peritoneal Dialysis (CAPD) for at least 3 months
3. 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
4. Have a blood hemoglobin concentration above 8,5 g/100ml (data will be verified with Investigators)
5. Have not experienced peritonitis episodes in the last 3 months
6. Be treated with Extraneal (nocturnal exchange bag solution) for at least 1 month
7. Be treated with 3 diurnal exchange bag solutions (1.5% or 2.5% glucose) and one nocturnal exchange bag solution (Extraneal)
8. Have Kt/V urea measurement > 1.7 per week in a previous test performed within 6 months that should be confirmed at Baseline Visit
9. Have a minimum weekly creatinine clearance of 45 litres in a previous test performed within 6 months that should be confirmed at Baseline Visit
10. 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
11. 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
12. Be treated by the participating clinical Investigator for a period of at least three months
13. Have understood and signed the Informed Consent Form.

Exclusion Criteria:

1. Have a history of drug or alcohol abuse in the six months prior to entering the protocol
2. Be in treatment with androgens
3. Have Diabetes Mellitus (as defined by the American Diabetes Society, objectively documented by a fasting plasma glucose and HbA1c determinations)
4. Have clinically significant abnormal liver function test (SGOT, SGPT, and gamma-GT > 2 times the upper normal limit)
5. Have acute infectious conditions (i.e.: pulmonary infection, acute hepatitis, high or low urinary tract infections, renal parenchymal infection, pericarditis, etc)
6. Have a history of congestive heart failure and clinically significant arrhythmia
7. Have an history of epilepsy or any NCS disease
8. Have malignancy within the past 5 years, including lymphoproliferative disorders
9. 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
10. Have a history of L-Carnitine therapy or use in the month prior to entering the protocol
11. Have used any investigational drug in the 3 months prior to entering the protocol
12. Be in pregnancy, lactation, fertility age without protection against pregnancy by adequate contraceptive means

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glucose solution	Drug: PD solution containing glucose; 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.; Other Names: Dianeal (Baxter)
Experimental: Glucose and L-carnitine solution	Drug: PD solution containing glucose and L-carnitine; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Iperboreal Pharma Srl
• Investigators: Study Director: Arduino Arduini, MD, Iperboreal Pharma Srl; Principal Investigator: Mario Bonomini, MD, G. d'Annunzio University

Publications and helpful links

General Publications

• Bonomini M, Di Liberato L, Del Rosso G, Stingone A, Marinangeli G, Consoli A, Bertoli S, De Vecchi A, Bosi E, Russo R, Corciulo R, Gesualdo L, Giorgino F, Cerasoli P, Di Castelnuovo A, Monaco MP, Shockley T, Rossi C, Arduini A. Effect of an L-carnitine-containing peritoneal dialysate on insulin sensitivity in patients treated with CAPD: a 4-month, prospective, multicenter randomized trial. Am J Kidney Dis. 2013 Nov;62(5):929-38. doi: 10.1053/j.ajkd.2013.04.007. Epub 2013 May 29.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2008
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: September 18, 2008
• First Submitted That Met QC Criteria: September 18, 2008
• First Posted (Estimate): September 19, 2008

Study Record Updates

• Last Update Posted (Actual): June 26, 2019
• Last Update Submitted That Met QC Criteria: June 24, 2019
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Insulin resistance; Dyslipidemia; L-carnitine; Peritoneal dialysis; Glucose homeostasis
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Hyperinsulinism; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Insulin Resistance; Pharmaceutical Solutions
• Other Study ID Numbers: IP-002-05