Effects of Mesna on Homocysteine in Kidney Failure

NCT ID: NCT00524199

Last Updated: 2018-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2007-06-30

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.

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.

Conditions

End Stage Renal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Saline IV infusion over five minutes at the beginning of dialysis.

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: OTHER

Saline IV infusion over five minutes at the beginning of dialysis thrice weekly.

Mesna

12 mg/kg mesna IV infusion over five minutes at the beginning of dialysis.

Group Type: ACTIVE_COMPARATOR

Mesna

Intervention Type: DRUG

12 mg/kg IV infusion over five minutes at the beginning of dialysis thrice weekly.

Interventions

Mesna

12 mg/kg IV infusion over five minutes at the beginning of dialysis thrice weekly.

Intervention Type: DRUG

Saline

Saline IV infusion over five minutes at the beginning of dialysis thrice weekly.

Intervention Type: OTHER

Other Intervention Names

Mesnex; Uromitexan

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David J Freeman, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Andrew A House, MD

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Locations

London Health Sciences Centre

London, Ontario, Canada

Countries

Canada

Other Identifiers

122006

Identifier Type: -

Identifier Source: secondary_id

R-06-472

Identifier Type: -

Identifier Source: org_study_id