Arteriovenous Fistula OcclusionPhase 2NCT03106948
Delivery of Inhibitors of Lysyl Oxidase (LysoLox) on Serial Angioplasty and Time to Restenosis
A Phase 2 study testing Ascorbic Acid and Cuprimine Oral Product in people with Arteriovenous Fistula Occlusion, run by Southeast Renal Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Arteriovenous Fistula Occlusion
- What is being tested?
- Ascorbic Acid and Cuprimine Oral Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2017to Mar 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Southeast Renal Research Institute
Chattanooga, Tennessee, 37408
James A Tumlin, MD, 423-826-8003, jamestumlinmd@nephassociates.com
Jeremy Whitson, 423-826-8003, jeremywhitson@nephassociates.com
About this study
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
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.
Read the 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.
- Conditions
- Arteriovenous Fistula Occlusion
- Being tested
- Placebo, Ascorbic Acid, Cuprimine Oral Product
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Subject will undergo endoluminal biopsy prior to angioplasty but will NOT undergo insertion of the ACT drug delivery catheter
Ascorbic AcidDrug
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
Cuprimine Oral ProductDrug
Also called D-Penicillamine
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Cuprimine Oral Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2017
- Study start1 Feb 2017
- Primary completion31 Jan 2018 (estimated)
- Study completionMar 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Arteriovenous Fistula OcclusionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Southeast Renal Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Dialysis Clinic, Inc.
- Responsible party
- Principal investigator, James A. Tumlin MD, Southeast Renal Research Institute
- Investigators
- James A Tumlin, MD, Principal investigator, Southeast Renal Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03106948
- Sponsor's protocol ID
- Lysyl Oxidase (LysoLox)
- Status last verified
- Sep 2017
- First submitted
- 15 Feb 2017
- Last updated
- 11 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03106948
- Acronym / sponsor ID
- Lysyl Oxidase (LysoLox)
- Conditions
- Arteriovenous Fistula Occlusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Southeast Renal Research InstituteUniversity, hospital or other
- Collaborators
- Dialysis Clinic, Inc.
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 31 Jan 2018 (estimated)
- Study completion
- Mar 2018 (estimated)
- First posted
- 11 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Low frequency angioplasty | Placebo comparator | Drug: PlaceboSubjects 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 |
| Moderate frequency angioplasty | Active comparator | Drug: Ascorbic AcidSubjects 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 | Active comparator | Drug: Cuprimine Oral ProductHigh 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 |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboSubject will undergo endoluminal biopsy prior to angioplasty but will NOT undergo insertion of the ACT drug delivery catheter | Drug | Low frequency angioplasty |
| Ascorbic AcidSubject 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 | Drug | Moderate frequency angioplasty |
| Cuprimine Oral ProductAlso: D-PenicillamineSubject 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 | Drug | High frequency angioplasty |
Primary outcome
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.
Time frame: 12 months
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James A Tumlin, MD principal investigator
Southeast Renal Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ascorbic Acid and Cuprimine Oral Product in people with Arteriovenous Fistula Occlusion, run by Southeast Renal Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact James A Tumlin, MD (423-290-0882, jamestumlinmd@nephassociates.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2017; AzTrials last refreshed its copy on 8 Nov 2026.