The Impact of Delflex on Mesothelial Cell Viability and Peritoneal Transport (Delflex)
Primary Purpose
End Stage Renal Disease
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Active Comparator: Conventional peritoneal dialysis solution
Experimental: Novel biocompatible dialysis solution
Sponsored by
About this trial
This is an interventional treatment trial for End Stage Renal Disease focused on measuring Peritoneal dialysis, Biocompatible dialysis fluid
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Conventional peritoneal dialysis solution
Novel biocompatible dialysis solution Delflex neutral pH
Arm Description
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.
Outcomes
Primary Outcome Measures
Mesothelial cell shedding and apoptosis
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
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)
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
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.
Full Information
NCT ID
NCT01292863
First Posted
February 8, 2011
Last Updated
February 1, 2013
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Fresenius Medical Care North America
1. Study Identification
Unique Protocol Identification Number
NCT01292863
Brief Title
The Impact of Delflex on Mesothelial Cell Viability and Peritoneal Transport
Acronym
Delflex
Official Title
The Impact of a Biocompatible Peritoneal Dialysis Solution (Delflex Neutral pH) on Mesothelial Cell Viability and Peritoneal Transport
Study Type
Interventional
2. Study Status
Record Verification Date
February 2013
Overall Recruitment Status
Withdrawn
Why Stopped
Study was modified to in vitro design and no longer involves participants
Study Start Date
March 2011 (undefined)
Primary Completion Date
February 2012 (Anticipated)
Study Completion Date
May 2012 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Fresenius Medical Care North America
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease
Keywords
Peritoneal dialysis, Biocompatible dialysis fluid
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Conventional peritoneal dialysis solution
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Novel biocompatible dialysis solution Delflex neutral pH
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
Active Comparator: Conventional peritoneal dialysis solution
Other Intervention Name(s)
Delflex
Intervention Description
Daily dialysis solution to be used for 3 months in crossover fashion.
Intervention Type
Other
Intervention Name(s)
Experimental: Novel biocompatible dialysis solution
Other Intervention Name(s)
Delflex neutral pH
Intervention Description
Daily dialysis solution to be used for 3 months in crossover fashion.
Primary Outcome Measure Information:
Title
Mesothelial cell shedding and apoptosis
Description
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Cancer antigen 125 (CA 125) in spent dialysate
Description
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.
Time Frame
6 months
Title
Characterize the mesothelial transport of glucose degradation products (GDPs) and advanced advanced glycosylation end products (AGEs)
Description
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.
Time Frame
6 months
Title
Connective tissue growth factor(CTGF)in spent dialysis fluid
Description
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.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cynthia J Denu-Ciocca, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
8706362
Citation
Davies SJ, Russell L, Bryan J, Phillips L, Russell GI. Impact of peritoneal absorption of glucose on appetite, protein catabolism and survival in CAPD patients. Clin Nephrol. 1996 Mar;45(3):194-8.
Results Reference
background
PubMed Identifier
11805177
Citation
Williams JD, Craig KJ, Topley N, Von Ruhland C, Fallon M, Newman GR, Mackenzie RK, Williams GT. Morphologic changes in the peritoneal membrane of patients with renal disease. J Am Soc Nephrol. 2002 Feb;13(2):470-479. doi: 10.1681/ASN.V132470.
Results Reference
background
PubMed Identifier
14870877
Citation
Williams JD, Craig KJ, von Ruhland C, Topley N, Williams GT; Biopsy Registry Study Group. The natural course of peritoneal membrane biology during peritoneal dialysis. Kidney Int Suppl. 2003 Dec;(88):S43-9. doi: 10.1046/j.1523-1755.2003.08805.x. No abstract available.
Results Reference
background
PubMed Identifier
18178947
Citation
Pajek J, Kveder R, Bren A, Gucek A, Ihan A, Osredkar J, Lindholm B. Short-term effects of a new bicarbonate/lactate-buffered and conventional peritoneal dialysis fluid on peritoneal and systemic inflammation in CAPD patients: a randomized controlled study. Perit Dial Int. 2008 Jan-Feb;28(1):44-52.
Results Reference
background
PubMed Identifier
15200450
Citation
Williams JD, Topley N, Craig KJ, Mackenzie RK, Pischetsrieder M, Lage C, Passlick-Deetjen J; Euro Balance Trial Group. The Euro-Balance Trial: the effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane. Kidney Int. 2004 Jul;66(1):408-18. doi: 10.1111/j.1523-1755.2004.00747.x.
Results Reference
background
PubMed Identifier
18300115
Citation
Theodoridis M, Passadakis P, Kriki P, Gioka T, Panagoutsos S, Mourvati E, Thodis E, Kantartzi K, Vargemezis V. The alteration of dialysate cancer antigen 125 concentration under a biocompatible bicarbonate peritoneal dialysis solution and the preservation of the mesothelial cell viability. Ren Fail. 2008;30(2):161-7. doi: 10.1080/08860220701808384.
Results Reference
background
PubMed Identifier
18552238
Citation
Kanjanabuch T, Siribamrungwong M, Khunprakant R, Kanjanabuch S, Jeungsmarn P, Achavanuntakul B, Pongpirul K, Park MS, Tungsanga K, Eiam-Ong S. Overnight mesothelial cell exfoliation: a magic tool for predicting future ultrafiltration failure in patients on continuous ambulatory peritoneal dialysis. Perit Dial Int. 2008 Jun;28 Suppl 3:S107-13.
Results Reference
background
PubMed Identifier
12787426
Citation
Zarrinkalam KH, Stanley JM, Gray J, Oliver N, Faull RJ. Connective tissue growth factor and its regulation in the peritoneal cavity of peritoneal dialysis patients. Kidney Int. 2003 Jul;64(1):331-8. doi: 10.1046/j.1523-1755.2003.00069.x.
Results Reference
background
PubMed Identifier
20015945
Citation
Mizutani M, Ito Y, Mizuno M, Nishimura H, Suzuki Y, Hattori R, Matsukawa Y, Imai M, Oliver N, Goldschmeding R, Aten J, Krediet RT, Yuzawa Y, Matsuo S. Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate. Am J Physiol Renal Physiol. 2010 Mar;298(3):F721-33. doi: 10.1152/ajprenal.00368.2009. Epub 2009 Dec 16.
Results Reference
background
PubMed Identifier
11929138
Citation
Ishibashi Y, Sugimoto T, Ichikawa Y, Akatsuka A, Miyata T, Nangaku M, Tagawa H, Kurokawa K. Glucose dialysate induces mitochondrial DNA damage in peritoneal mesothelial cells. Perit Dial Int. 2002 Jan-Feb;22(1):11-21.
Results Reference
background
PubMed Identifier
14531821
Citation
Morgan LW, Wieslander A, Davies M, Horiuchi T, Ohta Y, Beavis MJ, Craig KJ, Williams JD, Topley N. Glucose degradation products (GDP) retard remesothelialization independently of D-glucose concentration. Kidney Int. 2003 Nov;64(5):1854-66. doi: 10.1046/j.1523-1755.2003.00265.x.
Results Reference
background
PubMed Identifier
9663893
Citation
Linden T, Forsback G, Deppisch R, Henle T, Wieslander A. 3-Deoxyglucosone, a promoter of advanced glycation end products in fluids for peritoneal dialysis. Perit Dial Int. 1998 May-Jun;18(3):290-3.
Results Reference
background
PubMed Identifier
16419322
Citation
Thornalley PJ. Measurement of protein glycation, glycated peptides, and glycation free adducts. Perit Dial Int. 2005 Nov-Dec;25(6):522-33.
Results Reference
background
PubMed Identifier
14733914
Citation
Li W, Hamada Y, Nakashima E, Naruse K, Kamiya H, Akiyama N, Hirooka H, Takahashi N, Horiuchi S, Hotta N, Oiso Y, Nakamura J. Suppression of 3-deoxyglucosone and heparin-binding epidermal growth factor-like growth factor mRNA expression by an aldose reductase inhibitor in rat vascular smooth muscle cells. Biochem Biophys Res Commun. 2004 Feb 6;314(2):370-6. doi: 10.1016/j.bbrc.2003.12.095.
Results Reference
background
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The Impact of Delflex on Mesothelial Cell Viability and Peritoneal Transport
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