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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Ottawa Hospital Research Institute
Sponsor:
Collaborator:
Heart and Stroke Foundation of Ontario
Information provided by (Responsible Party):
Dr. Marcel Ruzicka, Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT01228279
First received: October 13, 2010
Last updated: October 16, 2013
Last verified: October 2013

October 13, 2010
October 16, 2013
July 2007
September 2014   (final data collection date for primary outcome measure)
  • Changes in muscle sympathetic nerve activity(MSNA) [ Time Frame: 6 weeks on PD and 18 weeks on PD ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    Plasma leptin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen
Same as current
Complete list of historical versions of study NCT01228279 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    *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 ] [ Designated as safety issue: No ]
    *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 ] [ Designated as safety issue: No ]
    *Plasma insulin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen
Same as current
Not Provided
Not Provided
 
Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
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.

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).

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
  • End-stage Renal Disease (ESRD)
  • Kidney Disease
  • 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 Name: Dextrose-based PD solution
  • 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 Name: Icodextrin-based PD solution
  • 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.
    Intervention: Other: DIANEAL
  • 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
    Intervention: Other: EXTRANEAL
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
December 2014
September 2014   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact: Marcel Ruzicka, MD 613-738-8400 ext 82748 mruzicka@ottawahospital.on.ca
Contact: Brendan McCormick, MD 613-738-8400 ext 82893 bmccormick@ottawahospital.on.ca
Canada
 
NCT01228279
NA6951
Yes
Dr. Marcel Ruzicka, Ottawa Hospital Research Institute
Ottawa Hospital Research Institute
Heart and Stroke Foundation of Ontario
Principal Investigator: Marcel Ruzicka, MD, PhD Ottawa Hospital Research Institute
Ottawa Hospital Research Institute
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP