Clinical trial NCT03106948: Delivery of Inhibitors of Lysyl Oxidase (LysoLox) on Serial Angioplasty and Time to Restenosis
Official title: Balloon Angioplasty of Dialysis AV Fistulae: Effect of Local Delivery of Inhibitors of Lysyl Oxidase (LysoLox) on Serial Angioplasty and Time to Restenosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Arteriovenous Fistula Occlusion
Lead sponsor: Southeast Renal Research Institute
Sponsor class: OTHER
Collaborators: name: Dialysis Clinic, Inc.
First posted: 2017-04-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: subjects will be assigned in an open labeled manner to Group 1 (Placebo), Group-2 (Ascorbic Acid), or Group-3 (Ascorbic acid \& D-penicillamine). Thus, there will be 10 placebo controls, 10 ascorbic acid patients, and 10 ascorbic acid and D-penicillamine patients. Subjects treated with ascorbic acid in combination with D-penicillamine may have the longest periods between serial angioplasties. Moreover, subjects receiving combination therapy may have greater post-angioplasty luminal diameters.
Primary purpose: TREATMENT

Brief summary: The narrowing of Dialysis Fistulae or Grafts is a near universal problem in patients with end-stage renal disease (ESRD) and requires patients to undergo repeated angioplasty or mechanical opening of the fistula.

Detailed description: The failure of dialysis accesses remains a leading cause of morbidity and medical costs among ESRD subjects. The underlying etiology for dialysis access failure is uniformly due to progressive narrowing of the vessel lumen leading to stasis and thrombosis of the access. The luminal narrowing of arteriovenous fistulae (AVFs) is due to progressive hyperplasia of vessel intima and subsequent infiltration of smooth muscle cells into the vessel media. Areas of stenosis within AVFs are characterized by dense neointimal hyperplasia, infiltration of vascular smooth muscle cells and expansion of extracellular matrix material. Additionally, varying types of vascular injury increase the rate of collagen and elastin deposition within the medial and serosal areas of the vessel.

Eligibility criteria: Inclusion Criteria:

* Age 18 and \< 90 years old
* Receiving stable out-subject hemodialysis for a minimum of 3 months
* Have a lower arm or upper arm AVF that has been cleared for use by the vascular surgeon or interventional nephrologist
* Have agreed to participate voluntarily and signed and dated an IRB approved, subject informed consent form
* Dysfunctional Dialysis Fistula: Any subject with

  * Two or more venous pressure readings exceeding 250 mmHg for a minimum of 5 minutes at a blood flow of 500mls/min within a single dialysis run AND a documented reduction in KT/V by \> 0.2; OR
  * Patients with venous pressures \> 250 mm Hg on two or more days within a 30 day period OR
  * Patients who on physical exam are found to have palpable obstructions, post-stenotic dilation of the access or evidence of prolonged post-dialysis bleeding.
* Any patient with one of the above conditions will be to have a dysfunctional AVF. This definition will be applied to the screening of study subjects as well as the determination of recurrent fistula dysfunction at 12 months.

Exclusion Criteria:

* Scheduled for surgical revision of the fistula;
* Have been in another investigational (non-approved) drug or device study within the previous 30 days;

  \*\*have a known allergy to any component of the investigational product (drug or device)
* Subjects with a "Hero Graft" will be excluded from the study
* Subjects having received a stent for correction of a prior stenosis will be excluded from the trial
* Subjects with more than \> 3 hemodynamically significant stenosis at one time (with the exception of a central venous stenosis)
* Subjects who are pregnant will be excluded from the trial (pregnancy test will be performed on subjects of child bearing potential). A urine pregnancy test will be utilized.

Primary outcomes:
measure: Patients treated with ascorbic acid in combination with D-penicillamine will have longer periods between serial angioplasties over 12-month period. Additionally, subjects receiving combination therapy may have greater post-angioplasty luminal diameters.
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
Study officials:
affiliation: Southeast Renal Research Institute
name: James A Tumlin, MD
role: PRINCIPAL_INVESTIGATOR
References: