Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction

This study has been completed.
Sponsor:
Collaborators:
Ministry of Health & Welfare, Korea
Fresenius Medical Care Korea
Information provided by:
Kyungpook National University
ClinicalTrials.gov Identifier:
NCT01315314
First received: March 11, 2011
Last updated: March 16, 2011
Last verified: April 2007

March 11, 2011
March 16, 2011
October 2005
April 2008   (final data collection date for primary outcome measure)
Inflammation-endothelial-dysfunction index (IEDI) [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
Inflammation-endothelial-dysfunction index (IEDI) is a composite score derived from measurement of serum levels of CRP (high sensitivity assay), soluble VCAM-1 and soluble ICAM-1. Changes between the groups will be tested by analysis of covariance (ANCOVA) with baseline values as covariates. Serial data will also be analyzed using a linear mixed model.
Inflammation-endothelial-dysfunction index (IEDI) [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
Inflammation-endothelial-dysfunction index (IEDI) is a composite score derived from measurement of serum levels of CRP (high sensitivity assay), soluble VCAM and soluble ICAM. Changes between the groups will be tested by analysis of covariance (ANCOVA) with baseline values as covariates. Serial data will also be analyzed using a linear mixed model. Survival analysis will be done by Kaplan-Meier survival analysis with Log-Rank test.
Complete list of historical versions of study NCT01315314 on ClinicalTrials.gov Archive Site
  • Individual component markers of IEDI [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    individual component markers of the IEDI including sICAM-1, sVCAM-1, and hs-CRP
  • RRF [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    residual renal function (RRF) as average of urea and creatinine clearances by 24 hour urine collection
  • peritoneal clearance [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    peritoneal clearance as weekly Kt/V urea and creatinine clearance
  • peritoneal ultrafiltration [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    peritoneal ultrafiltration volume
  • peritoneal transport status [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    dialysate-to-plasma ratio of creatinine at 4 hours of peritoneal equilibration test
  • serum albumin [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
  • LBM [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    lean body mass (LBM) estimated from creatinine kinetics
  • nPNA [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    normalized protein equivalent of nitrogen appearance (nPNA)
  • SGA [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    subjective global assessment (SGA) with a four item and seven-point scale
  • Blood pressure [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    systolic and diastolic blood pressure
  • use of antihypertensive medications [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    number of antihypertensive medications
  • peritonitis rates [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    peritonitis rates
  • technique survival [ Time Frame: 12months ] [ Designated as safety issue: No ]
    technique survival by Kaplan-Meier survival analysis with Log-Rank test.
  • patient survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    patient survival by Kaplan-Meier survival analysis with Log-Rank test.
Individual component markers of IEDI, RRF, LBM, nPCR and SGA [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
Secondary outcome variables are the individual component markers of the IEDI including sICAM-1, sVCAM-1, and hs-CRP, residual renal function (RRF) as average of urea and creatinine clearances, peritoneal clearance as weekly Kt/V urea and creatinine clearance, peritoneal ultrafiltration, and peritoneal transport status by PET. In addition, nutritional indices including serum albumin, lean body mass (LBM), normalized protein equivalent of nitrogen appearance (nPNA), and subjective global assessment (SGA) will be evaluated.
Not Provided
Not Provided
 
Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction
Effects of Neutral pH and Low Glucose Degradation Product-containing Peritoneal Dialysis Fluid on Systemic Markers of Inflammation and Endothelial Dysfunction: a Randomized, Controlled 1-year Follow-up Study

The purpose of this study is to evaluate the effects of neutral pH and low glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) on systemic inflammation and endothelial dysfunction markers in incident PD patients.

New peritoneal dialysis fluids (PDF) with neutral pH and low glucose degradation products (GDPs) are used in patients on peritoneal dialysis (PD). Low GDP fluids are reported to be more biocompatible than conventional PDF. Determination of biocompatibility has mainly focused on local peritoneal effects; recently, there has been interest in evaluating the systemic biocompatibility of these fluids.

In recent analyses of two retrospective cohorts of Korean PD patients, significant survival advantage was shown for patients treated with the biocompatible PDF compared to patients treated with conventional PDF. However, the mechanisms of survival advantage with low GPD PDF in these observational studies are difficult to assess. Additionally, it is not clear that new PDFs favorably impact risk markers of cardiovascular disease (CVD).

Epidemiologic studies identified an independent association between inflammation and risk of cardiovascular events and mortality; this association has been confirmed in patients with advanced chronic kidney diseases (CKD).Other evidence showed that clinically overt vascular events are preceded by endothelial dysfunction and increases in circulating markers of endothelial activation, including vascular cellular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1.Moreover, there is an association between inflammation and elevated levels of soluble VCAM-1 and ICAM-1 in patients with or at risk of atherosclerosis. Elevated levels of soluble adhesion molecules are found in ESRD patients, especially in patients with CVD and malnutrition.

The investigators hypothesized that conventional PDF as well as uremia itself lead to local peritoneal changes such as peritoneal neoangiogenesis and fibrosis, effects related to ultrafiltration failure and subsequently volume overload. In addition, direct effect of GDPs and/or increased systemic levels of AGEs activate endothelial cells and increase levels of vascular adhesion molecules and inflammation. Both local and systemic effects of PDF are possibly associated with increased cardiovascular risks and mortality in PD patients.

This study aims to examine the effects of neutral pH and low GDP-containing PDF on systemic inflammation and endothelial dysfunction in incident PD patients in a randomized, controlled study.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Kidney Failure, Chronic
  • Disorders Associated With Peritoneal Dialysis
Drug: Balance, Fresenius Medical Care, Germany
low glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF)
Other Name: Balance, Fresenius Medical Care
  • No Intervention: conventional PDF (Stay safe)
  • Active Comparator: low GDP PDF (Balance)
    Intervention: Drug: Balance, Fresenius Medical Care, Germany
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
146
April 2008
April 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male and female patients aged over 18 years and less than 75 years
  • Within 90 days of initiation of first renal replacement treatment for ESRD
  • Selected for maintenance management by CAPD
  • Having provided informed consent
  • Physically and mentally capable of performing the therapy

Exclusion Criteria:

  • Patients were excluded if deemed to have less than 80% likelihood of survival for at least 1 year
  • episodes of peritonitis within prior 30 days
  • any malignancy other than treated skin carcinoma
  • uncontrolled congestive heart failure
  • recent (within 60 days) myocardial infarction or cerebrovascular accident
  • active systemic vasculitic disease including systemic lupus erythematosus, polyarteritis nodosa, ANCA-nephritis, active rheumatoid disease, or active venous thrombotic-embolic disease
  • any acute infection at the time of enrollment
  • active or actively treated tuberculosis
  • recent (within 30 days) systemic bacterial infection.
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
 
NCT01315314
IEDI MCS, A084001
No
Yong-Lim, Kim, Division of Nephrology and Department of Internal Medicine, Kyungpook National University Hospital
Kyungpook National University
  • Ministry of Health & Welfare, Korea
  • Fresenius Medical Care Korea
Study Chair: Yong-Lim Kim, Professor Kyungpook National University
Kyungpook National University
April 2007

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