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

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Completed
• CT.gov ID: NCT02414204
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 2
• Duration (Months): 39
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Improve Endothelial Function and Decrease Vascular Stenosis	Drug: Sildenafil; Other: Placebo	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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 Start Date: Apr 1, 2015
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Jun 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
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.
Placebo Comparator: Placebo Placebo twice a day orally	Other: Placebo; Placebo will be over encapsulated to identical to drug comparison

Outcome Measures

Primary Outcome Measures

1. Change in Baseline and 2 Week FMD/VP Measurements Between Sildenafil Group and Placebo Group [2 weeks]

   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.

Secondary Outcome Measures

1. Number of Participants With a Change in Blood Flow Rate [6 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294

Sponsors and Collaborators

• University of Alabama at Birmingham

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 11, 2018

More Information

Publications

None provided.

• Responsible Party: Timmy Lee, MD, Principal investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT02414204
• Other Study ID Numbers: F150220002
• First Posted: Apr 10, 2015
• Last Update Posted: Aug 12, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Timmy Lee, MD, Principal investigator, University of Alabama at Birmingham: Arteriovenous Fistulas (AVFS); Hemodialysis Fistula Maturation (HFM); Flow-Mediated Dilation (FMD); Nitroglycerin-Mediated (NMD); Venous Plethysmography (VP)
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Arteriovenous Fistula; Fistula; Vascular Remodeling; Sildenafil Citrate

Study Results

Participant Flow

Arm/Group Title	Sildenafil	Placebo
Arm/Group Description	20 mg twice a day orally 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.	Placebo twice a day orally Placebo: Placebo will be over encapsulated to identical to drug comparison
Period Title: Overall Study
STARTED	2	2
COMPLETED	2	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sildenafil	Placebo	Total
Arm/Group Description	20 mg twice a day orally 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.	Placebo twice a day orally Placebo: Placebo will be over encapsulated to identical to drug comparison	Total of all reporting groups
Overall Participants	2	2	4
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	2 100%	4 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%	0 0%	1 25%
Male	1 50%	2 100%	3 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 100%	2 100%	4 100%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Baseline and 2 Week FMD/VP Measurements Between Sildenafil Group and Placebo Group
Description	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil	Placebo
Arm/Group Description	20 mg twice a day orally 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.	Placebo twice a day orally Placebo: Placebo will be over encapsulated to identical to drug comparison
Measure Participants	2	2
Mean (Standard Error) [Change in FMD%]	10.8 (8.0)	8.6 (2.9)

2. Secondary Outcome

Title	Number of Participants With a Change in Blood Flow Rate
Description	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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil	Placebo
Arm/Group Description	20 mg twice a day orally 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.	Placebo twice a day orally Placebo: Placebo will be over encapsulated to identical to drug comparison
Measure Participants	2	2
Count of Participants [Participants]	2 100%	1 50%

Adverse Events

Time Frame	Adverse events were collected from time of enrollment until 6 weeks following Arteriovenous Fistula (AVF) surgery
Arm/Group Title	Sildenafil		Placebo
Arm/Group Description	20 mg twice a day orally 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.		Placebo twice a day orally Placebo: Placebo will be over encapsulated to identical to drug comparison
All Cause Mortality
	Sildenafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Serious Adverse Events
	Sildenafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Sildenafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)

Limitations/Caveats

This was a pilot study. Only four participants were recruited during the study period.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.