The Impact of Delflex on Mesothelial Cell Viability and Peritoneal Transport

This study has been withdrawn prior to enrollment.
(Study was modified to in vitro design and no longer involves participants)
Sponsor:
Collaborator:
Fresenius Medical Care North America
Information provided by (Responsible Party):
Cindy Denu-Ciocca, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01292863
First received: February 8, 2011
Last updated: February 1, 2013
Last verified: February 2013
  Purpose

The purpose of this study is to evaluate the impact of Delflex neutral pH (a biocompatible peritoneal dialysis solution) on mesothelial cell viability and peritoneal transport.


Condition Intervention
End Stage Renal Disease
Other: Active Comparator: Conventional peritoneal dialysis solution
Other: Experimental: Novel biocompatible dialysis solution

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Impact of a Biocompatible Peritoneal Dialysis Solution (Delflex Neutral pH) on Mesothelial Cell Viability and Peritoneal Transport

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Mesothelial cell shedding and apoptosis [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    Mesothelial cell shedding has been recently reported to predict deterioration of the peritoneal membrane.The novel peritoneal dialysis solution, Delflex neutral pH solution may decrease peritoneal inflammatory response resulting in less mesothelial cell shedding and apoptosis in the peritoneal dialysis effluent compared to use with standard peritoneal dialysate.

    The primary specific aim of the current project is to compare the effect of Delflex neutral pH solution with conventional dialysis solution on mesothelial cell shedding and apoptosis



Secondary Outcome Measures:
  • Cancer antigen 125 (CA 125) in spent dialysate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Cancer antigen 125 (CA 125) is a marker of mesothelial cell mass and studies have shown significantly increased levels of CA 125 utilizing novel biocompatible peritoneal dialysis solutions compared to conventional solutions. We plan to determine whether CA 125 correlate with effluent total and apoptotic mesothelial cells.

  • Characterize the mesothelial transport of glucose degradation products (GDPs) and advanced advanced glycosylation end products (AGEs) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Theoretically, a promising benefit of utilizing the novel peritoneal dialysis solutions is the beneficial effect of reduced local and systemic damage secondary to advanced glycosylation products. A recent study found a significant decrease in circulating AGE levels in patients treated with low GDP solution over 3 months compared to levels after 3 months using standard peritoneal dialysis fluid. We plan to characterize the mesothelial transport of GDPs and AGEs after exposure to Delflex neutral pH solution versus conventional peritoneal dialysis solution.

  • Connective tissue growth factor(CTGF)in spent dialysis fluid [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Connective tissue growth factor (CTGF) levels in spent peritoneal dialysis fluid are strongly associated with high peritoneal solute transport rate and ultrafiltration failure. Connective tissue growth factor (CTFG) may be another marker of peritoneal membrane fibrosis and thus predictive of dialysis membrane failure. We plan to determine whether CTGF levels correlate with effluent total and apoptotic mesothelial cells.


Enrollment: 0
Study Start Date: March 2011
Estimated Study Completion Date: May 2012
Estimated Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Conventional peritoneal dialysis solution
Subjects will be randomized to perform dialysis with the conventional peritoneal dialysis solution for 3 months. At the end of three months mesothelial cell shedding and apoptosis will be measured.
Other: Active Comparator: Conventional peritoneal dialysis solution
Daily dialysis solution to be used for 3 months in crossover fashion.
Other Name: Delflex
Experimental: Novel biocompatible dialysis solution Delflex neutral pH Other: Experimental: Novel biocompatible dialysis solution
Daily dialysis solution to be used for 3 months in crossover fashion.
Other Name: Delflex neutral pH

Detailed Description:

In spite of its benefits, many peritoneal dialysis patients ultimately have to switch dialysis therapy to hemodialysis secondary to technique failure. Numerous etiologies for peritoneal dialysis treatment failure exist and include the continuous exposure of the peritoneal membrane to bioincompatible dialysis solutions with acidic pH and high content of glucose degradation products. These factors have been implicated in mesothelial cell loss, fibrosis and neovascularization, resulting in alterations in solute transport and ultrafiltration failure. Novel peritoneal dialysis solutions with neutral pH and low concentrations of glucose degradation products have recently been developed to improve biocompatibility and ameliorate the consequences of membrane damage with conventional peritoneal dialysis solutions. While novel peritoneal dialysis solutions have been available outside the United States for several years, Delflex Neutral pH has only recently been approved for use in the United States. Thus, the majority of all the data supporting the benefits of these novel solutions comes from locations outside of the United States.

The central question regarding the novel peritoneal dialysis solution is whether long term use will result in better preservation of the peritoneal membrane to support dialysis. Ultimately, this can only be determined with studies comparing long term outcomes of patients using the various solutions. However, given the expected availability in the United States and the potential benefits of the novel peritoneal dialysis solutions long term studies comparing outcomes with conventional solutions raises ethical concerns. Therefore, surrogate markers for peritoneal membrane integrity are necessary. Short term studies using various surrogate markers to assess mesothelial cell mass and peritoneal inflammation such as Cancer Antigen 125 (CA125) and pro-inflammatory cytokines have been reported, but it is uncertain how well these markers predict long term outcome. Recently, a novel approach to predict outcome has been reported, using mesothelial cell shedding and apoptosis. The number of mesothelial cells and the number of apoptotic mesothelial cells in a standard 8 hour dialysis dwell were reported to correlate well with deterioration of peritoneal dialysis characteristics over a one year follow-up. The authors concluded that mesothelial cell shedding and apoptosis are reliable predictors of peritoneal membrane deterioration.

The purpose of this study is to evaluate the impact of Delflex neutral pH (a biocompatible peritoneal dialysis solution) on mesothelial cell viability and peritoneal transport. The study will specifically compare mesothelial cell shedding and apoptosis in the peritoneal dialysis effluent after exposure to Delflex neutral pH solution and conventional peritoneal dialysis solution. Cancer Antigen 125 (CA125)levels (indicative of mesothelial cell mass) and connective tissue growth factor (CTGF) levels (a marker of inflammation) will be measured in the spent dialysate to determine whether these markers correlate with cell shedding and apoptosis. The study will also characterize the transport of glucose degradation products (GDPs) and advanced glycosylation end products (AGEs) across the mesothelial cells after exposure to Delflex neutral pH solution versus conventional peritoneal dialysis solution.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 18 years of age
  • Incident or prevalent patients with End Stage Kidney disease treated with either CAPD (continuous ambulatory peritoneal dialysis) or CCPD (continuous cycling peritoneal dialysis)
  • Patients must maintain modality of either CAPD or CCPD throughout duration of study
  • Able to provide informed consent

Exclusion Criteria:

  • Pregnant or lactating women
  • Recent (< 3 months) history of peritonitis
  • CCPD utilizing Baxter cycler (due to inability to connect Delflex solution to cycler)
  • Anticipated renal transplant within 6 months of enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01292863

Sponsors and Collaborators
University of North Carolina, Chapel Hill
Fresenius Medical Care North America
Investigators
Principal Investigator: Cynthia J Denu-Ciocca, MD University of North Carolina, Chapel Hill
  More Information

Publications:

Responsible Party: Cindy Denu-Ciocca, MD, Associate Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01292863     History of Changes
Other Study ID Numbers: 10-2359
Study First Received: February 8, 2011
Last Updated: February 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Peritoneal dialysis
Biocompatible dialysis fluid

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Dialysis Solutions
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014