Clinical trial NCT02164318: Effects of Exercise and Improved Nitric Oxide Bioavailability on Arteriovenous Fistula Maturation
Official title: Effects of Exercise and Improved Nitric Oxide Bioavailability on Arteriovenous Fistula Maturation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: End Stage Renal Disease
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2014-06-16
Enrollment: 11
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This project will examine if enhancing Nitric Oxide (NO) bioavailability increases the rates of arteriovenous fistula (AVF) maturation in end stage renal disease patients requiring vascular access for hemodialysis. To enhance NO bioavailability the study team will utilize a program of forearm exercise training, application of nitroglycerin ointment or both. Goals of this study are (A) to measure if recruited subjects can tolerate the intervention protocols, and determine if dependent variable measures, including surgery outcome, and measurement of physiologic and biologic markers, can be obtained; (B) To measure subject compliance and adherence rates for each of the intervention arms and testing visits; (C) To examine which intervention or combination of interventions demonstrates the strongest preliminary effects in order to estimate power for a pivotal intent to treat trial; and (D) explore group differences in clinical vascular markers and biologic markers in vein tissue.

Detailed description: This project will examine if enhancing Nitric Oxide (NO) bioavailability increases the rates of arteriovenous fistula (AVF) maturation in end stage renal disease patients requiring vascular access for hemodialysis. To enhance NO bioavailability the study team will utilize a program of forearm exercise training, application of nitroglycerin ointment or both.

Following entry into the study, approximately 4 weeks prior to surgery subjects will undergo a series of non-invasive tests of vascular function in the arm of fistula creation. Following this vascular function testing, subjects will follow the intervention treatment for 4 weeks. After 4 weeks of intervention treatment and prior to surgery, the vascular function analysis will be repeated to determine if the interventions had an effect on arm vascular function. Surgery to create the AVF will follow the second vascular function analysis. A discard sample of the vein used to create the AVF and a blood sample will be collected during surgery to assess potential biologic differences between intervention groups. The interventions will be continued until 4 weeks following surgery. Subjects will be followed to determine if the AVF matured and was successfully used for dialysis.

Eligibility criteria: Inclusion Criteria:

1. Life expectancy of at least 6 months
2. Chronic kidney disease with anticipated start of hemodialysis within six months or current hemodialysis dependence.
3. Ability to understand and comply with the requirements of the entire study and communicate with the study team.
4. Written informed consent using a document that has been approved by the Duke Human Institutional Review Board.
5. If female and of childbearing potential (premenopausal and not surgically sterile) must have a negative pregnancy test and be willing to use contraception until completion of 8 weeks of intervention. This will include abstinence, barrier methods, hormones, or intra-uterine device.

Exclusion Criteria:

1. Patients currently on medication that is contraindicated with nitropaste, including isosorbide nitrate therapy, nitroglycerin, minoxidil, or PDE inhibitors (i.e. Sildenafil).
2. Patients with a diastolic blood pressure below 65 or a systolic blood pressure below 90.
3. Patients with a history of illicit drug use in the previous 5 years.
4. Patients who would require AVF placement before completion of the initial 4 weeks of intervention therapy
5. Patients who are otherwise are not suitable for 8 weeks of handgrip training or nitropaste therapy.
6. Patients under the 18 of age are not eligible for nitropaste interventions

Primary outcomes:
measure: Count of Participants With Mature Arteriovenous Fistula (AVF)
timeFrame: 3 month post surgery to create AVF
Secondary outcomes:
measure: Count of Participants With a Patent Fistula
timeFrame: 3 months post surgery
measure: Count of Participants Using Their AVF for Dialysis
timeFrame: 12 months post surgery
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: Jeffrey H Lawson, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: