Effects of Mesna on Homocysteine in Kidney Failure

November 2, 2018 updated by: Lawson Health Research Institute

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

Intervention / Treatment

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: Four weeks
Four weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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