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Completed

NCT Number: NCT01228279

Sympathetic Activity in Patients With End-stage Renal Disease 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.

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Key information

Conditions

End-stage Renal Disease (ESRD) Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Disease Kidney Diseases Kidney Failure, Chronic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Dianeal

Other

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

EXTRANEAL

Other

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

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

Sponsors and collaborators

Lead sponsor

Ottawa Hospital Research Institute

Other

Collaborators

  • Heart and Stroke Foundation of Ontario

Registry information

Official study 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

Acronym: SAPD

Important dates

Study start
2007
Primary completion
2018
Study completion
2018
First posted
Oct 26, 2010
Registry last updated
Mar 15, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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