Effects of Exercise and Improved Nitric Oxide Bioavailability on Arteriovenous Fistula Maturation

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.

Study Overview

• Status: Terminated
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: Nitroglycerin ointment; Other: Handgrip training

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Standard of care
Experimental: Handgrip training group; Perform isometric handgrip exercises for 15 minutes twice per day for a total of 30 minutes	Other: Handgrip training
Experimental: Nitroglycerin ointment group; Apply 15mg of nitroglycerin ointment to the back of the hand of the surgical arm nightly	Drug: Nitroglycerin ointment; Other Names: Nitropaste
Experimental: Combined handgrip training /Nitroglycerin ointment group; Perform isometric handgrip exercises for 15 minutes twice each day for a total of 30 minutes and apply 15mg of nitroglycerin ointment to the back of the hand of the surgical arm nightly	Drug: Nitroglycerin ointment; Other Names: Nitropaste; Other: Handgrip training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of Participants With Mature Arteriovenous Fistula (AVF)	Use of AVF for dialysis for dialysis dependent participants, or fistula deemed mature based on physical exam in predialysis participants (diameter >6 mm, blood flow >600 ml by ultrasound or estimated by physical exam).	3 month post surgery to create AVF

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of Participants With a Patent Fistula	Determination that AVF is patent (has blood flow, no occlusion).	3 months post surgery
Count of Participants Using Their AVF for Dialysis	Successful use of AVF at 12 months in dialysis dependent patients. Not relevant in participants that are predialysis or that discontinue dialysis prior to AVF use.	12 months post surgery

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Jeffrey H Lawson, MD/PhD, Duke Health

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): February 18, 2016
• Study Completion (Actual): March 10, 2017

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: June 12, 2014
• First Posted (Estimate): June 16, 2014

Study Record Updates

• Last Update Posted (Actual): July 12, 2017
• Last Update Submitted That Met QC Criteria: June 16, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Renal Insufficiency; Pathological Conditions, Anatomical; Renal Insufficiency, Chronic; Cardiovascular Abnormalities; Vascular Malformations; Arteriovenous Malformations; Vascular Fistula; Kidney Failure, Chronic; Fistula; Arteriovenous Fistula; Vasodilator Agents; Nitroglycerin
• Other Study ID Numbers: Pro00054388; R21DK103082 (U.S. NIH Grant/Contract)