Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis (SAPD)
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.
|End-stage Renal Disease (ESRD) Kidney Disease||Other: DIANEAL Other: EXTRANEAL||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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|
- Changes in muscle sympathetic nerve activity(MSNA) [ Time Frame: 6 weeks on PD and 18 weeks on PD ]
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
- Changes in leptin levels [ Time Frame: 6 weeks on PD and 18 weeks on PD ]Plasma leptin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen
- Changes in blood pressure as assessed from 24-hour ambulatory blood pressure monitor (ABPM) [ Time Frame: 6 weeks on PD and 18 weeks on PD ]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
- Changes in extracellular volume assessed by bioelectrical impedance (BIA) [ Time Frame: 6 weeks on PD and 18 weeks on PD ]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.
- Changes in heart rate variability [ Time Frame: 6 weeks on PD and 18 weeks on PD ]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.
- Changes in central intravascular volume assessed by cardiac ultrasound [ Time Frame: 6 weeks on PD and 18 weeks on PD ]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
- Changes in plasma catecholamines levels [ Time Frame: 6 weeks on PD and 18 weeks on PD ]*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
- Changes in BNP (Brain Natriuretic Peptide)levels [ Time Frame: 6 weeks on PD and 18 weeks on PD ]*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
- Changes in plasma insulin levels [ Time Frame: 6 weeks on PD and 18 weeks on PD ]*Plasma insulin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen
|Study Start Date:||July 2007|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||January 2018 (Final data collection date for primary outcome measure)|
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.
Weeks 1 to 6 (6 weeks):
Weeks 7 to 18 (12 weeks):
*same regimen as weeks 1 to 6, for both CAPD and CCPD patients
Other Name: 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
Weeks 1 to 6 (6 weeks):
Weeks 7 to 18 (12 weeks):
Other Name: Icodextrin-based PD solution
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01228279
|Contact: Marcel Ruzicka, MD||613-738-8400 ext email@example.com|
|Contact: Brendan McCormick, MD||613-738-8400 ext firstname.lastname@example.org|
|Ottawa Hospital Research Institute||Recruiting|
|Ottawa, Ontario, Canada|
|Contact: Marcel Ruzicka, MD 613-738-8400 ext 82748 email@example.com|
|Contact: Brendan McCormick, MD 613-738-8400 ext 82893 firstname.lastname@example.org|
|Principal Investigator: Marcel Ruzicka, MD, PhD|
|Sub-Investigator: Brendan McCormick, MD|
|Sub-Investigator: Frans Leenen, MD|
|Sub-Investigator: Kathryn Ascah, MD|
|Sub-Investigator: Greg Knoll, MD|
|Principal Investigator:||Marcel Ruzicka, MD, PhD||Ottawa Hospital Research Institute|