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

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.

Study Overview

• Status: Completed
• Conditions: Improve Endothelial Function and Decrease Vascular Stenosis
• Intervention / Treatment: Drug: Sildenafil; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥19 years of age male or female
2. Chronic Kidney Disease Stage IV or V patients or End Stage Renal Disease Patient requiring arteriovenous fistula surgery

Exclusion Criteria:

1. Patient currently on nitrate therapy or any nitric oxide donor in any form
2. Patient currently on protease inhibitor or non-nucleoside reverse transcriptase inhibitor
3. Patient with resting systolic blood pressure <90 mm Hg and diastolic blood pressure < 50 mm Hg.
4. Patient life expectancy < nine months.
5. Patient unable or unwilling to meet study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo twice a day orally	Other: Placebo; Placebo will be over encapsulated to identical to drug comparison
Active Comparator: Sildenafil; 20 mg twice a day orally	Drug: Sildenafil; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Timmy Lee, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: April 7, 2015
• First Posted (Estimate): April 10, 2015

Study Record Updates

• Last Update Posted (Actual): August 12, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Arteriovenous Fistulas (AVFS); Hemodialysis Fistula Maturation (HFM); Flow-Mediated Dilation (FMD); Nitroglycerin-Mediated (NMD); Venous Plethysmography (VP)
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Congenital Abnormalities; Renal Insufficiency; Pathological Conditions, Anatomical; Cardiovascular Abnormalities; Vascular Malformations; Arteriovenous Malformations; Vascular Fistula; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Fistula; Arteriovenous Fistula; Vascular Remodeling; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: F150220002