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Delivery of Inhibitors of Lysyl Oxidase (LysoLox) on Serial Angioplasty and Time to Restenosis

Primary Purpose

Arteriovenous Fistula Occlusion

Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
Ascorbic Acid
Cuprimine Oral Product
Sponsored by
Southeast Renal Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Arteriovenous Fistula Occlusion

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Southeast Renal Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Low frequency angioplasty

Moderate frequency angioplasty

High frequency angioplasty

Arm Description

Subjects who have had 0-1 angioplasty during the 12 months prior to randomization. Subjects will have endoluminal biopsy prior to angioplasty but will not have insertion of the ACT drug delivery catheter

Subjects who have had 2-3 angioplasties during the 12 months prior to randomization. Subjects will have endoluminal biopsy prior to angioplasty followed by insertion of the ACT drug delivery catheter where ascorbic acid (10.0 µM) will be injected following conventional balloon angioplasty

High frequency angioplasty defined by 4 or more angioplasties 12 months prior to randomization. Subjects will receive ascorbic acid (10.0 µM) in combination with D-penicillamine (25 µM) will be injected following conventional balloon angioplasty

Outcomes

Primary Outcome Measures

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.
Subjects are followed for 12 months and monitored for signs of fistula dysfunction. When the patient's fistula becomes dysfunctional they will be referred for a fistulogram. The time between serial fistulograms will be recorded as a secondary endpoint. Patients who are referred for a repeat fistulogram and having a luminal narrowing of greater than 70% will undergo a second intimal biopsy.

Secondary Outcome Measures

Full Information

First Posted
February 15, 2017
Last Updated
September 6, 2017
Sponsor
Southeast Renal Research Institute
Collaborators
Dialysis Clinic, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03106948
Brief Title
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

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2017 (Actual)
Primary Completion Date
January 31, 2018 (Anticipated)
Study Completion Date
March 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Southeast Renal Research Institute
Collaborators
Dialysis Clinic, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arteriovenous Fistula Occlusion

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low frequency angioplasty
Arm Type
Placebo Comparator
Arm Description
Subjects who have had 0-1 angioplasty during the 12 months prior to randomization. Subjects will have endoluminal biopsy prior to angioplasty but will not have insertion of the ACT drug delivery catheter
Arm Title
Moderate frequency angioplasty
Arm Type
Active Comparator
Arm Description
Subjects who have had 2-3 angioplasties during the 12 months prior to randomization. Subjects will have endoluminal biopsy prior to angioplasty followed by insertion of the ACT drug delivery catheter where ascorbic acid (10.0 µM) will be injected following conventional balloon angioplasty
Arm Title
High frequency angioplasty
Arm Type
Active Comparator
Arm Description
High frequency angioplasty defined by 4 or more angioplasties 12 months prior to randomization. Subjects will receive ascorbic acid (10.0 µM) in combination with D-penicillamine (25 µM) will be injected following conventional balloon angioplasty
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subject will undergo endoluminal biopsy prior to angioplasty but will NOT undergo insertion of the ACT drug delivery catheter
Intervention Type
Drug
Intervention Name(s)
Ascorbic Acid
Intervention Description
Subject will undergo endoluminal biopsy prior to angioplasty followed by insertion of the ACT drug delivery catheter where ascorbic acid (10.0 µM) will be injected following conventional balloon angioplasty
Intervention Type
Drug
Intervention Name(s)
Cuprimine Oral Product
Other Intervention Name(s)
D-Penicillamine
Intervention Description
Subject will undergo endoluminal biopsy prior to angioplasty followed by insertion of the ACT drug delivery catheter where ascorbic acid (10.0 µM) in combination with D-penicillamine (25 µM) will be injected following conventional balloon angioplasty
Primary Outcome Measure Information:
Title
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.
Description
Subjects are followed for 12 months and monitored for signs of fistula dysfunction. When the patient's fistula becomes dysfunctional they will be referred for a fistulogram. The time between serial fistulograms will be recorded as a secondary endpoint. Patients who are referred for a repeat fistulogram and having a luminal narrowing of greater than 70% will undergo a second intimal biopsy.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
James A Tumlin, MD
Phone
423-290-0882
Email
jamestumlinmd@nephassociates.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jeremy Whitson
Phone
423-826-8003
Email
jwhitson@nephassociates.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James A Tumlin, MD
Organizational Affiliation
Southeast Renal Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southeast Renal Research Institute
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37408
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James A Tumlin, MD
Phone
423-826-8003
Email
jamestumlinmd@nephassociates.com
First Name & Middle Initial & Last Name & Degree
Jeremy Whitson
Phone
423-826-8003
Email
jeremywhitson@nephassociates.com
First Name & Middle Initial & Last Name & Degree
James A Tumlin, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Delivery of Inhibitors of Lysyl Oxidase (LysoLox) on Serial Angioplasty and Time to Restenosis

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