Phosphodiesterase Type 5 Inhibition to Improve Endothelial Function and Vascular Remodeling in Chronic Kidney Disease and End Stage Renal Disease Patients Requiring New Arteriovenous Fistula

Study Overview
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Brief Summary
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Patients with stage IV and V chronic kidney disease and end stage renal disease requiring hemodialysis at University of Alabama at Birmingham (UAB) Dialysis Clinics will be recruited from the UAB Vascular Access Clinic, which has been the site for recruitment of patients requiring new vascular access for the last 10 years.

Detailed Description
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The main purpose of this research study is to conduct a research study to determine if Sildenafil compared to placebo will improve the vascular health of arteries and veins before arteriovenous fistula creation (shunt) and how quickly your veins and arteries dilate and increase in blood flow after fistula creation. An arteriovenous fistula (shunt) is a connection between the artery and vein in the arm for dialysis use. Another purpose of this study is to determine if Sildenafil reduces the blood and tissue levels of oxidants prior to fistula creation. Oxidants are harmful substances in the body that damage the cells tissues, and organs.

Official Title
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Phosphodiesterase Type 5 Inhibition to Improve Endothelial Function and Vascular Remodeling in Chronic Kidney Disease and End Stage Renal Disease Patients Requiring New Arteriovenous Fistula

Conditions
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Improve Endothelial Function and Decrease Vascular Stenosis

Intervention / Treatment
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* Drug: Sildenafil
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥19 years of age male or female Chronic Kidney Disease Stage IV or V patients or End Stage Renal Disease Patient requiring arteriovenous fistula surgery Exclusion Criteria: Patient currently on nitrate therapy or any nitric oxide donor in any form Patient currently on protease inhibitor or non-nucleoside reverse transcriptase inhibitor Patient with resting systolic blood pressure <90 mm Hg and diastolic blood pressure < 50 mm Hg. Patient life expectancy < nine months. Patient unable or unwilling to meet study requirements.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 99 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sildenafil<br>20 mg twice a day orally | Drug: Sildenafil<br>* Sildenafil, a phosphodiesterase 5 inhibitor that enhances the effects of nitric oxide (NO), has been shown in experimental and clinical studies in cardiovascular disease to improve endothelial function and decrease vascular stenosis.<br>|
| Placebo Comparator: Placebo<br>Placebo twice a day orally | Other: Placebo<br>* Placebo will be over encapsulated to identical to drug comparison<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Baseline and 2 Week FMD/VP Measurements Between Sildenafil Group and Placebo Group | For flow mediated dilation studies (FMD), the brachial artery diameter was measured by ultrasound at baseline. An automated floor pressure cuff was inflated on the upper arm to a suprasystolic pressure that was sustained for 5 minutes, and the brachial diameter measurement was repeated 55-65 seconds after releasing the cuff. FMD was calculated as the percentage change in arterial diameter from baseline. For venous occlusion plethysmography studies (VP), forearm volume was measured using a strain-gauge plethysmography device during application of an upper arm BP cuff at increasing but subsystolic pressures. Venous capacitance slope was estimated from the volume-pressure relationship and expressed as a percentage increase in volume per millimeters of mercury. The change at baseline and 2 weeks in these measurements between the sildenafil and placebo group will be assessed. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Change in Blood Flow Rate | Blood flow of the fistula at 6 weeks is measured with doppler ultrasound and values of the fistula artery and vein are obtained (ml/min). The difference in blood flow rates of the fistula artery and vein between the sildenafil treated group and placebo group will be assessed. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arteriovenous Fistulas (AVFS), Hemodialysis Fistula Maturation (HFM), Flow-Mediated Dilation (FMD), Nitroglycerin-Mediated (NMD), Venous Plethysmography (VP)