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

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT01228279

Collaborator

Heart and Stroke Foundation of Ontario (Other)

Enrollment

Location

Arms

137

Actual Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
End-stage Renal Disease (ESRD) Kidney Disease	Other: DIANEAL Other: EXTRANEAL	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

50 participants

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

Actual Study Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Dec 1, 2018

Actual Study Completion Date :

Dec 1, 2018

Arms and Interventions

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

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

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

Outcome Measures

Primary Outcome Measures

Changes in muscle sympathetic nerve activity(MSNA) [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 [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

Secondary Outcome Measures

Changes in blood pressure as assessed from 24-hour ambulatory blood pressure monitor (ABPM) [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) [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 [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 [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 [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 [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 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)