Improve Endothelial Function and Decrease Vascular Stenosis
Conditions
Keywords
Arteriovenous Fistulas (AVFS), Hemodialysis Fistula Maturation (HFM), Flow-Mediated Dilation (FMD), Nitroglycerin-Mediated (NMD), Venous Plethysmography (VP)
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.
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.
Interventions
DRUGSildenafil
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.
OTHERPlacebo
Placebo will be over encapsulated to identical to drug comparison
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 99 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil 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. | 2 |
| Placebo Placebo twice a day orally
Placebo: Placebo will be over encapsulated to identical to drug comparison | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Sildenafil | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 0 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
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.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil | Change in Baseline and 2 Week FMD/VP Measurements Between Sildenafil Group and Placebo Group | 10.8 Change in FMD% | Standard Error 8 |
| Placebo | Change in Baseline and 2 Week FMD/VP Measurements Between Sildenafil Group and Placebo Group | 8.6 Change in FMD% | Standard Error 2.9 |
Secondary
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.
Time frame: 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sildenafil | Number of Participants With a Change in Blood Flow Rate | 2 Participants |
| Placebo | Number of Participants With a Change in Blood Flow Rate | 1 Participants |