Ascorbic Acid on Restenosis of Dysfunctional Hemodialysis Vascular Access

Effect of Ascorbic Acid Administration on Restenosis of Dysfunctional Hemodialysis Vascular

To investigate the effect of ascorbic acid on angiographic restenosis after percutaneous transluminal angioplasty (PTA) for dysfunctional dialysis vascular access.

Study Overview

• Status: Completed
• Conditions: Hemodialysis Access Failure
• Intervention / Treatment: Drug: Ascorbic Acid 300 MG; Drug: Ascorbic Acid 600 MG; Drug: Normal saline

Detailed Description

Vascular access dysfunction is the leading cause of treatment insufficiency or interruption among hemodialysis (HD) patients, and it is responsible for a large portion of the cost of any end-stage renal disease (ESRD) program. Intimal hyperplasia at the venous segment of vascular access is the characteristic lesion, which leads to dysfunction or failure of both arteriovenous fistulas (AVF) and prosthetic grafts (AVG). Although percutaneous transluminal angioplasty (PTA) is effective in treating these stenotic lesions, the effect seems not permanent and restenosis after PTA remains a major problem. A number of studies have examined the clinical, anatomical, and technical factors for restenosis, the causes of restenosis are still not fully understood.This highlights a possible role of non-traditional risk factors to explain the high restenosis rate at the venous segment of vascular access, which includes oxidative stress, inflammation, and endothelial dysfunction.

Ascorbic acid (vitamin C) is a potent antioxidant used for a long time. Hemodialysis patients had been shown to be deficient in antioxidant defense, which resulted in increasing requirement of ascorbic acid supplement. Currently, intravenous 300-mg ascorbic acid supplementation three times a week after hemodialysis had been used to overcome erythropoietin resistance in patients with iron deficiency. Theoretically, ascorbic acid scavenges reactive oxygen species and reactive nitrogen species and may thereby prevent oxidative injuries. Investigators reported that administration of high dose ascorbic acid could prevent lipid peroxidation and oxidative DNA damage in patients with ESRD.

In this study, the investigators investigated whether ascorbic acid could decrease venous restenosis after PTA for dysfunctional hemodialysis vascular access.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical signs, i.e., decreased thrill, development of collateral veins, limb swelling, and prolonged bleeding from puncture sites, suggesting vascular access dysfunction
• reduction of flow rate more than 25% from baseline
• total access blood flow rate less than 500 mL/min by ultrasound dilution method
• increased venous pressure during dialysis, as dynamic venous pressure exceeding threshold levels of 150 mmHg in AVF and 160 mmHg in AVG, respectively, under dialysis blood flow 250 ml/min for three consecutive times

Exclusion Criteria:

• hospitalized for infection, heart failure, or acute coronary syndrome in recent 3 months
• unable to comply with follow-up visits
• already under ascorbic acid or other antioxidant supplements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ascorbic acid 300 mg; Ascorbic acid 300 mg was administered intravenously for 5 minutes after each dialysis session, three times per week for 12 weeks.	Drug: Ascorbic Acid 300 MG; Ascorbic acid 300 mg was administered intravenously for 5 minutes after each dialysis session, three times per week for 12 weeks.; Other Names: Vitamin C
Active Comparator: Ascorbic acid 600 mg; Ascorbic acid 600 mg was administered intravenously for 5 minutes after each dialysis session, three times per week for 12 weeks.	Drug: Ascorbic Acid 600 MG; Ascorbic acid 600 mg was administered intravenously for 5 minutes after each dialysis session, three times per week for 12 weeks.; Other Names: Vitamin C
Placebo Comparator: Placebo; Normal saline was administered intravenously for 5 minutes after each dialysis session, three times per week for 12 weeks.	Drug: Normal saline; Normal saline was administered intravenously for 5 minutes after each dialysis session, three times per week for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the extent of restenosis after angioplasty	the extent of restenosis defined by the late loss of minimal vessel diameter and late loss of percentage stenosis at follow-up angiograms	12 weeks

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital Hsin-Chu Branch
• Investigators: Study Director: Chih-Cheng Wu, M.D., Associate professor of Medicine, National Taiwan University, College of Medicine, Taipei, Taiwan

Publications and helpful links

General Publications

• Tomoda H, Yoshitake M, Morimoto K, Aoki N. Possible prevention of postangioplasty restenosis by ascorbic acid. Am J Cardiol. 1996 Dec 1;78(11):1284-6. doi: 10.1016/s0002-9149(96)00613-3.
• Yang CW, Wu CC, Luo CM, Chuang SY, Chen CH, Shen YF, Tarng DC. A randomized feasibility study of the effect of ascorbic acid on post-angioplasty restenosis of hemodialysis vascular access (NCT03524846). Sci Rep. 2019 Jul 31;9(1):11095. doi: 10.1038/s41598-019-47583-w.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: April 30, 2018
• First Submitted That Met QC Criteria: May 13, 2018
• First Posted (Actual): May 15, 2018

Study Record Updates

• Last Update Posted (Actual): May 15, 2018
• Last Update Submitted That Met QC Criteria: May 13, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Ascorbic acid; restenosis; hemodialysis vascular access
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Antioxidants; Vitamins; Ascorbic Acid
• Other Study ID Numbers: 99G002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No