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

NCT03106948 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: Lysyl Oxidase (LysoLox)
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Arteriovenous Fistula Occlusion

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Study Arms (3)

Low frequency angioplasty

PLACEBO COMPARATOR

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

Drug: Placebo

Moderate frequency angioplasty

ACTIVE COMPARATOR

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

Drug: Ascorbic Acid

High frequency angioplasty

ACTIVE COMPARATOR

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

Drug: Cuprimine Oral Product

Interventions

Placebo DRUG

Subject will undergo endoluminal biopsy prior to angioplasty but will NOT undergo insertion of the ACT drug delivery catheter

Low frequency angioplasty

Ascorbic Acid DRUG

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

Moderate frequency angioplasty

Cuprimine Oral Product DRUG

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

Also known as: D-Penicillamine

High frequency angioplasty

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Southeast Renal Research Institute: lead
• Dialysis Clinic, Inc.: collaborator

Study Sites (1)

Southeast Renal Research Institute

Chattanooga, Tennessee, 37408, United States

RECRUITING

MeSH Terms

Interventions

Ascorbic Acid; Penicillamine

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• James A Tumlin, MD

  Southeast Renal Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James A Tumlin, MD

CONTACT

423-290-0882; jamestumlinmd@nephassociates.com

Jeremy Whitson

CONTACT

423-826-8003; jwhitson@nephassociates.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: February 15, 2017
• First Posted: April 11, 2017
• Study Start: February 1, 2017
• Primary Completion: January 31, 2018
• Study Completion: March 1, 2018
• Last Updated: September 11, 2017

Record last verified: 2017-09

Locations

US (1)