The Impact of Delflex on Mesothelial Cell Viability and Peritoneal Transport

NCT ID: NCT01292863

Last Updated: 2013-02-04

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2012-05-31

Brief Summary

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.

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.

Conditions

End Stage Renal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Active Comparator: Conventional peritoneal dialysis solution

Intervention Type: OTHER

Daily dialysis solution to be used for 3 months in crossover fashion.

Novel biocompatible dialysis solution Delflex neutral pH

Group Type: EXPERIMENTAL

Experimental: Novel biocompatible dialysis solution

Intervention Type: OTHER

Daily dialysis solution to be used for 3 months in crossover fashion.

Interventions

Active Comparator: Conventional peritoneal dialysis solution

Daily dialysis solution to be used for 3 months in crossover fashion.

Intervention Type: OTHER

Experimental: Novel biocompatible dialysis solution

Daily dialysis solution to be used for 3 months in crossover fashion.

Intervention Type: OTHER

Other Intervention Names

Delflex; Delflex neutral pH

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fresenius Medical Care North America

INDUSTRY

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Cindy Denu-Ciocca, MD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cynthia J Denu-Ciocca, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

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Other Identifiers

10-2359

Identifier Type: -

Identifier Source: org_study_id