Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis (SAPD)

Effects of Non-Glucose-Based Peritoneal Dialysis Solution "EXTRANEAL" on Changes in Leptin Levels and Sympathetic Activity Induced by Conventional Glucose-Based Dialysate "DIANEAL" in Patients on Peritoneal Dialysis

Hypothesis:

Patients starting peritoneal dialysis with a glucose-based regimen have high sympathetic activity in response to an increase in leptin and insulin. Converting patients from a regimen of only glucose containing dialysate to a regimen with non-glucose-based solution, icodextrin, will reduce the insulin and leptin levels and will reverse dialysis-induced increases in sympathetic activity.

Study Overview

• Status: Completed
• Conditions: End-stage Renal Disease (ESRD); Kidney Disease
• Intervention / Treatment: Other: DIANEAL; Other: EXTRANEAL

Detailed Description

Cardiovascular mortality remains higher among patients treated with peritoneal dialysis as compared to patients treated with hemodialysis. Sympathetic hyperactivity is considered a significant emerging risk factor for cardiovascular mortality among patients with ESRD (End-Stage Renal Disease). Sympathetic activity, via its hemodynamic effects and trophic effects, and in interaction with RAAS (Renin Angiotensin Aldosterone System), does play a major role in cardiac and vascular remodelling, development of LVH and vascular hypertrophy, as well as progression to CHF. Glucose-based dialysate induces hyperinsulinemia and hyperleptinemia. We propose that hyperleptinemia induced by glucose-based peritoneal solution is a significant contributing factor to sympathetic hyperactivity in ESRD patients treated with PD, and could be prevented by non-glucose-based PD solution such as icodextrin-based.

Adult patients with ESRD starting PD as their first renal replacement therapy modality will be studied. Patients will be recruited 1-3 weeks prior to starting PD treatment. At baseline, specific studies for microneurography (MSNA), fasting plasma insulin, leptin, catecholamines and brain natriuretic peptide (BNP) will be performed. EKG will be recorded and digitized for further assessment of heart rate variability using power spectral analysis. Extracellular fluid volume status will be assessed by bioelectrical impedance. Central vascular volume will be assessed from inferior vena cava (IVC) by heart ultrasound. Consequently 24-h ambulatory blood pressure monitoring(ABPM)and a 24-h urine collection for urea clearance and creatinine clearance will be done.

All participants into the study will receive a PD treatment for 6 weeks with standard glucose-based PD solution Dianeal. The specific studies are repeated at 6 weeks.Then, patients will be randomized to one of the two groups (arms). One group will continue with Dianeal PD solution for another 12 weeks. The other group will receive Dianeal during the day and Extraneal, icodextrin or non-glucose based solution, during the night only, for the next 12 weeks. The specific studies are repeated at 12 weeks after randomization (18 weeks of PD treatment).

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada
      • Ottawa Hospital Research Institute

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:

• Adult (age 18 years and older)
• Patients with end-stage renal disease(ESRD)/chronic kidney disease(CKD)stage 5

Exclusion Criteria:

• Diabetes Mellitus
• Acute coronary syndrome in the past 6 months
• Cardiac arrhythmias (2nd and 3rd degree heart block or premature ventricular complexes in Lown classes 4 or 5)
• Symptoms suggestive of obstructive or central sleep apnea (with a score of > 10 on Epworth sleepiness scale)
• Patients taking Clonidine
• Body mass index (BMI) > 34
• Patients unable to give consent
• Pregnant women
• Patients with leg injury involving nerve damage
• Patients taking anticoagulant medication
• Patients with significant bleeding disorder or liver disorder
• Hemoglobin <1.05 g/dl at the time of initiation of therapy
• patients with unilateral or bilateral nephrectomy
• Planned kidney transplant in the next 4 months
• Life expectancy under 6 months
• Oliguria (urine output less than 400 ml per day)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DIANEAL; One group of patients will start peritoneal dialysis with the glucose-based solution (DIANEAL) for 6 weeks, then will continue with the same type of solution for another 12 weeks.	Other: DIANEAL; Weeks 1 to 6 (6 weeks): CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of DIANEAL during the night; CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 4-6 hour dwells of DIANEAL during the day and three to seven 2-4-hour dwells of DIANEAL during the night Weeks 7 to 18 (12 weeks): *same regimen as weeks 1 to 6, for both CAPD and CCPD patients; Other Names: Dextrose-based PD solution
Active Comparator: EXTRANEAL; The other group of patients will start peritoneal dialysis with the glucose-based solution (DIANEAL) for 6 weeks, then will continue with DIANEAL solution during the day and the non-glucose-based solution, EXTRANEAL, during the night	Other: EXTRANEAL; Weeks 1 to 6 (6 weeks): CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of DIANEAL during the night; CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and three to seven 2-4-hour dwells of DIANEAL during the night Weeks 7 to 18 (12 weeks): CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of EXTRANEAL during the night; CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and one 8-12-hour dwell of EXTRANEAL during the night; Other Names: Icodextrin-based PD solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in muscle sympathetic nerve activity(MSNA)	Muscle sympathetic nerve activity(MSNA) is measured by microneurography at; baseline (before starting peritoneal dialysis); 6 weeks of PD; 18 weeks of PD(12 weeks after randomization) MSNA increases on a glucose-based dialysis regimen and may decrease by adding non-glucose-based solution	6 weeks on PD and 18 weeks on PD
Changes in leptin levels	Plasma leptin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen	6 weeks on PD and 18 weeks on PD

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in blood pressure as assessed from 24-hour ambulatory blood pressure monitor (ABPM)	Blood pressure will be assessed with 24-hour ABPM at baseline, 6 weeks on PD and 18 weeks after starting peritoneal dilaysis. Summary measures of each day and night period include average systolic and diastolic BP as well as % nocturnal dipping. These summary measures can predict cardiovascular events more accurately than casual BP measures	6 weeks on PD and 18 weeks on PD
Changes in extracellular volume assessed by bioelectrical impedance (BIA)	Bioelectrical impedance directly measures extracellular fluid volume and total body water. The test is based on the ability to detect differences in the conductive properties of a cell by measuring its resistance (impedance) to electrical current. The technique is reliable for tracking sequential changes in extracellular fluid volume.	6 weeks on PD and 18 weeks on PD
Changes in heart rate variability	During the microneurography testing, EKG is recorded. Heart rate and heart rate variability(HRV) will be analyzed from EKG data at baseline, 6 weeks and 18 weeks after starting dialysis.	6 weeks on PD and 18 weeks on PD
Changes in central intravascular volume assessed by cardiac ultrasound	Central intravascular volume will be assessed by measuring inferior vena cava (IVC) diameter during cardiac ultrasound at baseline, 6 weeks and 18 weeks on dialysis treatment	6 weeks on PD and 18 weeks on PD
Changes in plasma catecholamines levels	*Plasma catecholamines (epinephrine and norepinephrine) increase on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen	6 weeks on PD and 18 weeks on PD
Changes in BNP (Brain Natriuretic Peptide)levels	*Brain Natriuretic Peptide (BNP)increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen	6 weeks on PD and 18 weeks on PD
Changes in plasma insulin levels	*Plasma insulin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen	6 weeks on PD and 18 weeks on PD

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Heart and Stroke Foundation of Ontario
• Investigators: Principal Investigator: Marcel Ruzicka, MD, PHD, Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2007
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: October 13, 2010
• First Submitted That Met QC Criteria: October 22, 2010
• First Posted (Estimate): October 26, 2010

Study Record Updates

• Last Update Posted (Actual): March 15, 2021
• Last Update Submitted That Met QC Criteria: March 11, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Peritoneal Dialysis; Dialysis Solutions; Artificial Kidney; Renal Replacement Therapy; Renal Dialysis; Sympathetic Nervous System; Leptin; Icodextrin
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Dialysis Solutions; Pharmaceutical Solutions; Icodextrin
• Other Study ID Numbers: NA6951

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No