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Icodextrin Effects on Glucose Transporter Activation and Mediators of Fibrosis

NCT02133313 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 49

Last updated 2017-04-19

No results posted yet for this study

Summary

The time on peritoneal dialysis may be limited for a significant number of patients that use this modality of renal replacement therapy due to the inability of the peritoneal membrane to clear solutes or achieve adequate ultrafiltration, termed peritoneal membrane failure (PMF). This can be devastating for patients who have become accustomed to the quality of life provided by peritoneal dialysis and who otherwise have done well on this therapy. There is clinical evidence suggesting that icodextrin preserves the peritoneal membrane transport characteristics which may be linked to reduced cumulative glucose exposure of the peritoneal mesothelial cells. Theories to explain the role of dextrose in PMF have focused for the most part on the high intracellular concentrations of glucose without consideration to the potential pathogenic role of the glucose transporters which allow glucose entry into the cell. Experimental evidence in non-mesothelial cell lines indicate that some cellular processes that occur under high glucose conditions may not be related to intracellular glucose metabolism but to the type of glucose transporter allowing glucose entry. 3,4 However, little is known about these glucose transporters in peritoneal mesothelial cells and their potential role in the development of PMF.

We hypothesize the following

* The presence of Sodium Glucose Co-transporter (SGLT1) on peritoneal mesothelial cells plays a role in PMF under hyperglycemic conditions.
* Regulation of pro-fibrotic mediators such as reactive oxidative species,transforming growth factor β, and vascular endothelial growth factor are modulated by SGLT1 activation by glucose rather than glucose metabolism or concentration.
* Icodextrin does not activate the SGLT1 transporter establishing a mechanism that may explain the beneficial effects of icodextrin on peritoneal membrane transport.

Conditions

Sponsors & Collaborators

  • Baxter Healthcare Corporation

    collaborator INDUSTRY

  • University of Alabama at Birmingham

    lead OTHER

Principal Investigators

  • Eric L Wallace, M.D. · University of Alabama at Birmingham

Eligibility

Min Age
19 Years
Max Age
100 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-05-31
Primary Completion
2017-03-31
Completion
2017-03-31

Countries

  • United States

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02133313 on ClinicalTrials.gov