Effect of an L-Carnitine-Containing Peritoneal Dialysis (PD) Solution on Insulin Sensitivity in Diabetic 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 evaluated by measuring insulin requirement.

Study Overview

• Status: Withdrawn
• Conditions: Diabetes; End Stage Renal Disease
• Intervention / Treatment: Drug: PD Solution; Drug: PD solution containing L-carnitine

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70124
    • Renal, Dialysis and Transplant Unit, University of Bari
  • Chieti, Italy, 66100
    • Division of Nephrology, University of "G. d'Annunzio"
  • Desio, Italy, 20100
    • Nephrology and Dialysis Unit, Desio Hospital
  • Giulianova, Italy, 64021
    • Nephrology and Dialysis Unit, "Maria SS dello Splendore" 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
  • Teramo, Italy, 64100
    • Division of Nephrology and Dialysis, "Mazzini" 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. 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)
4. 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
5. Have a blood hemoglobin concentration above 8,5 g/100ml (data will be verified with Investigators)
6. Have not experienced peritonitis episodes in the last 3 months
7. Be treated with Extraneal (nocturnal exchange bag solution) for at least 1 month
8. Be treated with 3 diurnal exchange bag solutions (solution bags with 1.5% or 2.5% glucose) and one nocturnal exchange bag solution (Extraneal)
9. Have Kt/V urea measurement > 1.7 per week in a previous test performed within 3 months that should be confirmed at Baseline Visit
10. Have a minimum weekly creatinine clearance of 45 litres in a previous test performed within 6 months that should be confirmed at Baseline Visit
11. 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
12. 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
13. Be treated by the participating clinical Investigator for a period of at least three months
14. 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. Type 2 Diabetic patients under oral antidiabetic treatment with HbA1C < 8.5%
3. Be in treatment with androgens
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 CNS 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
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: A	Drug: PD Solution; 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.
Experimental: B	Drug: PD solution containing 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 180 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 measuring insulin requirement	time 0, 6 months

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Iperboreal Pharma Srl
• Investigators: Principal Investigator: Francesco P Schena, MD, University of Bari; Study Director: Arduino Arduini, MD, Iperboreal Pharma Srl

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Anticipated): October 1, 2013
• Study Completion (Anticipated): December 1, 2013

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: Diabetes; 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-003-05