Effects of Mesna on Homocysteine in Kidney Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00524199
Recruitment Status : Completed
First Posted : September 3, 2007
Last Update Posted : September 3, 2007
Canadian Institutes of Health Research (CIHR)
Information provided by:
Lawson Health Research Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
End Stage Renal Disease Drug: Mesna Other: Saline Phase 2

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  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of 12 mg/kg Intravenous Mesna on Plasma Total Homocysteine Concentration in Patients With End-Stage Renal Disease Requiring Hemodialysis
Study Start Date : March 2007
Actual Study Completion Date : June 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Failure
Drug Information available for: Mesna
U.S. FDA Resources

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

Primary Outcome Measures :
  1. Difference in plasma total homocysteine between placebo and mesna treatments [ Time Frame: Four weeks ]

Secondary Outcome Measures :
  1. Excretion of mesna during hemodialysis [ Time Frame: duration of dialytic session ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00524199

Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 5A5
Sponsors and Collaborators
Lawson Health Research Institute
Canadian Institutes of Health Research (CIHR)
Principal Investigator: David J Freeman, MSc, PhD Lawson Health Research Institute
Principal Investigator: Andrew A House, MD Lawson Health Research Institute Identifier: NCT00524199     History of Changes
Other Study ID Numbers: R-06-472
First Posted: September 3, 2007    Key Record Dates
Last Update Posted: September 3, 2007
Last Verified: August 2007

Keywords provided by Lawson Health Research Institute:

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Protective Agents
Physiological Effects of Drugs