Effects of Mesna on Homocysteine in Kidney Failure

The Effects of 12 mg/kg Intravenous Mesna on Plasma Total Homocysteine Concentration in Patients With End-stage Renal Disease Requiring Hemodialysis

The purpose of this research study is to examine the effect of a drug called mesna on the removal of homocysteine from blood during dialysis. Homocysteine is an amino acid (protein building block) found in the blood of all people, however it is considerably elevated in dialysis patients. People with increased levels of homocysteine in their blood are at increased risk of developing plaque buildup in their arteries and other related problems such as heart attack and stroke. This study will determine if mesna can improve the rate of homocysteine removal from blood during dialysis.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Other: Saline; Drug: Mesna

Detailed Description

Homocysteine is a thiol amino acid derived from dietary methionine. Elevated plasma total homocysteine (tHcy), termed hyperhomocysteinemia, is a graded, independent risk factor for the development of atherosclerosis. Elevated plasma tHcy can be normalized by supplementation with folic acid and vitamins B6 and B12 in most patients with normal renal function and this treatment has been shown to halt the progression of atherosclerotic plaque.

Over 90% of patients with end-stage renal disease (ESRD) requiring hemodialysis have elevated plasma tHcy. The leading causes of morbidity and mortality in these patients are cardiovascular-related pathologies such as myocardial infarction and stroke. Vitamin supplementation consistently fails to normalize elevated plasma tHcy in patients with ESRD, thus leaving them at increased risk. Plasma tHcy is 70 - 80% covalently protein bound limiting the effectiveness of dialysis as a tHcy lowering treatment.

Mesna (sodium 2-mercaptoethanesulfonic acid) is a thiol-containing drug currently indicated to prevent hemorrhagic cystitis associated with ifosfamide chemotherapy. Mesna has incidentally been shown to deplete plasma thiols in cancer patients undergoing ifosfamide chemotherapy. Mesna acts to exchange with thiols bound to plasma proteins enhancing their renal excretion. In vitro studies in our laboratory have shown that mesna rapidly (within 5 minutes) exchanges with protein bound homocysteine yielding a significantly larger dialyzable fraction of the thiol amino acid.

A pilot study recently completed by our group demonstrated a significant decrease in tHcy in eight hemodialysis patients receiving 12 mg/kg mesna three times a week pre-dialysis for one week. Although this therapy did cause a significant decline in tHcy, mesna failed to reduce tHcy to normal levels. The cumulative effects of mesna administration over a longer treatment period should be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with end-stage renal disease who have received hemodialysis thrice weekly for at least 90 days
• Serum albumin > 30 g/L.

Exclusion Criteria:

• Patients who refuse to sign a letter of informed consent
• Women who are or are trying to become pregnant or are breast-feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline IV infusion over five minutes at the beginning of dialysis.	Other: Saline; Saline IV infusion over five minutes at the beginning of dialysis thrice weekly.
Active Comparator: Mesna; 12 mg/kg mesna IV infusion over five minutes at the beginning of dialysis.	Drug: Mesna; 12 mg/kg IV infusion over five minutes at the beginning of dialysis thrice weekly.; Other Names: Mesnex; Uromitexan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in plasma total homocysteine between placebo and mesna treatments	Four weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Excretion of mesna during hemodialysis	duration of dialytic session

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: David J Freeman, MSc, PhD, Lawson Health Research Institute; Principal Investigator: Andrew A House, MD, Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2007
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: August 30, 2007
• First Submitted That Met QC Criteria: August 31, 2007
• First Posted (Estimate): September 3, 2007

Study Record Updates

• Last Update Posted (Actual): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 2, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: hemodialysis; homocysteine; mesna
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Physiological Effects of Drugs; Protective Agents; Mesna
• Other Study ID Numbers: R-06-472; 122006

Drug and device information, study documents

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