Icodextrin Study to Test Short-Term Safety, Tolerability and Preliminary Efficacy of Sodium-Free Solution in PD Patients

Study Overview
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Brief Summary
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Patients with kidney failure rely on dialysis for sodium and fluid removal. The importance of a sodium and fluid balance in patients with kidney disease is very important. Excess volume has been consistently associated with cardiovascular morbidity and mortality. Many peritoneal dialysis (PD) patients need large volumes of dextrose or Icodextrin based solutions to achieve fluid removal. Commonly used PD solutions also have high sodium concentrations to limit sugar absorption. These PD fluids can reduce the amount of sodium removed and may eventually lead to water retention over time with possible adverse outcomes. This research study is being conducted to determine if a single eight-hour dwell of intraperitoneal sodium-free 30% Icodextrin / 10% Dextrose solution is safe, tolerable and effective in achieving sodium and volume removal in PD patients.

Detailed Description
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This study is a phase 1 interventional study in Peritoneal Dialysis Patients. Investigators will recruit 10 participants. This study involves one visit at the London Health Sciences Centre University Hospital lasting approximately 9 hours. Study participants will receive one in-center PD dwell, consisting of peritoneal instillation of a sodium-free 30% Icodextrin/10% dextrose solution via their Tenckhoff catheter; the solution will be dwelling in the study participant's peritoneal cavity for a maximum of 8 hours as tolerated, at the end of which the solution will be drained. Participants will be monitored during administration of the study solution, during dwell and up to one hour after the Peritoneal Dialysis fluid is drained. Study participants will also undergo: Clinical blood pressure and heart rate monitoring: baseline + every 15 minutes for the first two hours; then every 30 minutes up until 1 hour post complete peritoneal solution drain Continuous Finapress hemodynamic monitoring (until 1 hour post peritoneal solution drain) Pain Monitoring throughout the study visit (Five point verbal scale and McGill Pain Questionnaire) Blood collection: baseline, 1, 2, 4, 8 hours into the dwell and 1 hour after the end of drain Peritoneal dialysate collection: 1, 2, 4, 8 hours into the dwell Urine collection throughout visit.

Official Title
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A Phase 1 Interventional Study to Test Short-Term Safety, Tolerability and Preliminary Efficacy of Sodium-Free Intraperitoneal 30% Icodextrin/10% Dextrose Solution in Peritoneal Dialysis Patients

Conditions
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Chronic Kidney Failure

Intervention / Treatment
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* Drug: Icodextrin/Dextrose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Functioning Tenckhoff catheter Stable PD prescription regimen (continuous ambulatory PD or automated PD) for the past month Age 18 years or older Willing and able to provide informed consent Able to Speak and Read English Exclusion Criteria: Type 1 or uncontrolled diabetes mellitus Active infections Pre-study serum sodium <130 mmol/L Serum bicarbonate < 18mmol/L Patients with standard PD prescriptions relying exclusively on lowest glucose containing fluid Allergy to starch-based polymers (e.g. corn starch) and/or icodextrin Intolerance to maltose or isomaltose Glycogen storage disease Uncorrectable mechanical defects that prevent effective PD or increase the risk of infection Documented loss of peritoneal function or extensive adhesions that compromise peritoneal function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Interventional Model Description: Single-arm, Open Label, Phase 1 Interventional study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intraperitoneal infusion with 500 mL of sodium-free 30% Icodextrin/ 10% Dextrose solution | Drug: Icodextrin/Dextrose<br>* Single 8 hour dwell of a 500mL intraperitoneal sodium-free 30% Icodextrin / 10% Dextrose solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment related Adverse Events or Serious Adverse Events. | Adverse Events and Serious Adverse Events will help determine the safety of the intraperitoneal solution. Change in symptoms from baseline. | Throughout the study visit - approximately 9 hours | 
| Changes in hemodynamic stability (Blood Pressure) | This will determine participant tolerability of the treatment. Systolic and Diastolic blood pressure (mm/Hg) will be measured throughout the study visit at baseline, every 15 minutes for 2 hours, then every 30 minutes until 1 hour after solution drain is complete. If the systolic or diastolic blood pressure changes more then 40 mmHg or more at any time point the study physician will be consulted for direction. | Throughout the study visit - approximately 9 hours | 
| Changes in hemodynamic stability (Heart Rate) | This will determine participant tolerability of the treatment. We will monitor heart rate (bpm) at baseline, every 15 minutes for 2 hours, then every 30 minutes until 1 hour after solution drain is complete. If heart rate is less then 50 beats per minute or greater then 120 beats per minute the study physician will be alerted. | Throughout the study visit - approximately 9 hours | 
| Changes in hemodynamic stability (Finapres monitoring) | This will determine tolerability of the treatment. Hemodynamic monitoring using Finapres (finger-cuff to detect beat-to-beat changes) Hemodynamic variables such as pulse rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance are derived. (for post hoc observational analysis only) | Throughout the study visit - approximately 9 hours | 
| Sodium Removal | This will measure the efficacy of the treatment. Serum sodium (mmol/L) levels will be drawn at baseline, 1, 2, 4, 8 and 9 hours and sent to the lab for analysis. | Throughout the study visit - approximately 9 hours | 
| Pain Assessment (Five-point Verbal Scale) | This pain assessment will determine tolerability of the treatment. Five-point Verbal Scale (0-no pain, 1=mild pain, 2=moderate pain, 3=severe pain, 4=very severe pain) We will complete the Five-point Verbal Scale at the following time points: start of infusion at 1, 3, and 5 minutes after start of infusion and at end of infusion of the Icodextrin/Dextrose solution 15, 30 minutes into dwell, hourly during dwell and at the end of dwell of the Icodextrin/Dextrose solution start of drain, 5 minutes into drain and end of drain of the Icodextrin/Dextrose solution If Five-Point verbal scale >3 for two consecutive readings and if pain exceeds individual tolerability, fluid will be drained and the study physician will be alerted. | Throughout the study visit - approximately 9 hours | 
| Pain Assessment (McGill Pain Questionnaire) | This pain assessment will determine tolerability of the treatment. McGill Pain Questionnaire (MPQ) 30 minutes into dwell of the Icodextrin/Dextrose solution The MPQ explores the multi-dimensional nature of pain. | Throughout the study visit - approximately 9 hours | 
| Ultrafiltration Volume | This will measure the efficacy of the treatment. Ultrafiltrate will be measured in litres post drain. | Throughout the study visit - approximately 9 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Glucose monitoring and glucose absorption | This will measure glucose (mmol/L) levels will be drawn at baseline, 1, 2, 4, 8 and 9 hours and sent to the lab for analysis. | Throughout the study visit - approximately 9 hours | 
| Dialysate icodextrin biproducts | This will measure the efficacy of the treatment. A 15 ml sample of peritoneal effluent will be collected at 1, 2, 4 and 8 hours in to dwell. This sample will be sent to the lab for the analysis of dialysate Icodextrin biproducts. | Throughout the study visit - approximately 9 hours | 
| Serum Icodextrin biproducts | This will measure the efficacy of the treatment. Serum will be collected at baseline, 1, 2, 4 and 8 and 9 hours and sent to lab for analysis of Icodextrin biproducts. | Throughout the study visit - approximately 9 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peritoneal Dialysis