Icodextrin Effects on Glucose Transporter Activation and Mediators of Fibrosis

April 17, 2017 updated by: Eric Wallace, University of Alabama at Birmingham

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.

Study Overview

Status

Completed

Conditions

Detailed Description

Participants enrolled in this study will have pertinent clinical information entered into a database. Participants will then have spent peritoneal dialysate collected at least every 6 months and analyzed for markers of fibrosis. Patients undergoing a special type of peritoneal dialysis start call urgent start peritoneal dialysis will have spent peritoneal dialysate collected more frequently at the start of peritoneal dialysis and then every 6 months. The results from the analysis of the peritoneal dialysate will then be correlated with data in the patient registry.

Quality assurance- As this is a single center trial all data will be monitored by the PI. Data will be entered in a prospective manner into the database by a research coordinator. Every 6 months data will be checked for accuracy by comparing to data collected for routine clinical purposes by both the home dialysis unit which tracks all hospitalizations, peritonitis, exit site infections, technique failures. As well as the dialysis access database maintained by the University of Alabama at Birmingham.

Source data verification- Data will come from both the history and physical of the primary investigator as well as electronic medical records at the University of Alabama at Birmingham and Falcon Electronic Health Record from Davita.

Data Dictionary is as follows. Variable / Field Name study_id Is the patient restarting Peritoneal dialysis after stopping If the patient is restarting are they restarting with the same catheter or a new catheter Date of 1st Access Length of time catheter placed prior to use How was the catheter placed: Surgically vs. Interventional Radiology Open versus laparoscopic Lysis of Adhesions Omentopexy Type of PD Catheter Has the patient had a second access procedure Medical Record Number Davita Medical Record Number Person Entering Data first_name last_name Date of Birth sex race address Is the patient new to dialysis? Has the patient previously been on peritoneal dialysis. transfer Why was peritoneal dialysis stopped. Type of Start: Urgent start versus traditional start Anuric Urgent Start: Inpatient or Outpatient Admit Date for PD Initiation Date of Discharge for pd initiation Did the patient require hemodialysis during urgent start period Indication for Hemodialysis Number of Hemodialysis sessions Nonsurgical catheter issues Date of PD start Age at PD start Date of PD graduation Length of time to PD graduation Reason for Urgent start PD first_dialysis_modality Predialysis education type_predialysis_education Glomerular filtration rate at time of PD start Has the patient stopped PD Did the patient stop Peritoneal dialysis or did they transfer out? Date PD was stopped Length of time on dialysis Age PD stopped Reason PD stopped When the patient transferred, did they transfer with an access or a permacath Cause of death Cause of End Stage Renal Disease (ESRD) Comorbidities Has the patient had a kidney transplant Previous abdominal surgeries? Type of previous abdominal surgeries height Indication for Peritoneal Equilibration Test (PET Date of PET Type of PET 2 hour D/P Creatinine 4 hour D/P Creatinine Transporter type 2 hour D/D0 Glucose 4 hour D/D0 Glucose Initial PET glucose PD Glucose 4 hours Glucose Absorption PET Drain Volume Ultrafiltration PD Sodium 0 Hour PD Sodium 1 Hour PD Sodium 2 hour PD Sodium 4 Hour Serum Sodium Minimum PD Sodium Level Systolic Blood Pressure Diastolic Blood Pressure Mean Arterial Pressure Weight Body Mass Index Hemoglobin Albumin Ferritin Iron Transferrin Saturation Hemoglobin A1c Creatinine Potassium BUN Sodium Hco3 Total Protein total cholesterol HDL LDL Vitamin D 25 Phosphorus Calcium PTH Kt/V Does the patient have a last fill Icodextrin versus dianeal Midday Total Liters per day Total Liters Total 6 month glucose exposure Is the patient on icodextrin Date of Icodextrin start Length of time on icodextrin Kt/v prior to icodextrin Kt/V after icodextrin Reason icodextrin stopped Date Icodextrin stopped Length of time on icodextrin Has the patient had peritonitis Date of infection Polymicrobial Pathogen Gram Positive Methicillin Resistant Gram Negative Ciprofloxacin Resistant Fungal Did the patient have antibiotics prior to fungal peritonitis What antibiotic Did the patient receive fungal prophylaxis Is this relapsing or recurrent Has the patient been hospitalized Date of admission Length of time to first admission Date of Discharge Length of stay Reason for admit Hospitalization Outcome Cause of death

Standard Operating Procedures: Patient recruitment will be from the University of Alabama at Birmingham Home Dialysis unit.

Sample size: As there are no data on which to base the power calculation for this unique study on glucose transporters and their role in peritoneal membrane fibrosis, descriptive statistics will be used to gain insight into the proposed research questions. Continuous variables will be summarized with mean and standard deviation or median and interquartile range depending on the distribution. Categorical variables will be summarized with frequency and percentage.

Study Type

Observational

Enrollment (Actual)

49

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham Home Dialysis Unit (Red Mountain Home Dialysis)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All patients over the age of 19 on Peritoneal Dialysis at the University of Alabama at Birmingham

Description

Inclusion Criteria:

  • 19 years of age or older
  • On Peritoneal Dialysis

Exclusion Criteria:

  • none

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Peritoneal Dialysis Patients
Patients on Peritoneal Dialysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in glucose transporter expression on peritoneal mesothelial cells
Time Frame: baseline to 3 years
baseline to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alabama at Birmingham

Collaborators

Baxter Healthcare Corporation

Investigators

  • Principal Investigator: Eric L Wallace, M.D., University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2014

Primary Completion (Actual)

March 1, 2017

Study Completion (Actual)

March 1, 2017

Study Registration Dates

First Submitted

April 30, 2014

First Submitted That Met QC Criteria

May 6, 2014

First Posted (Estimate)

May 8, 2014

Study Record Updates

Last Update Posted (Actual)

April 19, 2017

Last Update Submitted That Met QC Criteria

April 17, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICO-X140206005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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