Effects of Mesna on Homocysteine in Kidney Failure

This study has been completed.
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by:
Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT00524199
First received: August 30, 2007
Last updated: August 31, 2007
Last verified: August 2007
  Purpose

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 Intervention Phase
End Stage Renal Disease
Drug: Mesna
Other: Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Lawson Health Research Institute:

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

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

Enrollment: 10
Study Start Date: March 2007
Study Completion Date: June 2007
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00524199

Locations
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 5A5
Sponsors and Collaborators
Lawson Health Research Institute
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
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00524199     History of Changes
Other Study ID Numbers: R-06-472, 122006
Study First Received: August 30, 2007
Last Updated: August 31, 2007
Health Authority: Canada: Health Canada

Keywords provided by Lawson Health Research Institute:
homocysteine
hemodialysis
mesna

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

ClinicalTrials.gov processed this record on August 28, 2014