End Stage Renal DiseasePhase 2NCT00524199
Effects of Mesna on Homocysteine in Kidney Failure
A Phase 2 study testing Mesna and Saline in people with End Stage Renal Disease, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- End Stage Renal Disease
- What is being tested?
- Mesna and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2007to Jun 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with end-stage renal disease who have received hemodialysis thrice weekly for at least 90 days
- Serum albumin > 30 g/L.
Who cannot join
- Patients who refuse to sign a letter of informed consent
- Women who are or are trying to become pregnant or are breast-feeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Being tested
- Mesna, Saline
- Keywords
- homocysteine, hemodialysis, mesna
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MesnaDrug
Also called Mesnex, Uromitexan
12 mg/kg IV infusion over five minutes at the beginning of dialysis thrice weekly.
SalineOther
Saline IV infusion over five minutes at the beginning of dialysis thrice weekly.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Saline IV infusion over five minutes at the beginning of dialysis. Receives: Other: Saline |
| Mesna | Active comparator | 12 mg/kg mesna IV infusion over five minutes at the beginning of dialysis. Receives: Drug: Mesna |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in plasma total homocysteine between placebo and mesna treatments
Measured: Four weeks
Secondary outcomes (1)
Excretion of mesna during hemodialysis
Measured: duration of dialytic session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2007 (estimated)
- Study startMar 2007
- Study completionJun 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- David J Freeman, MSc, PhD, Principal investigator, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sAndrew A House, MD, Principal investigator, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00524199
- Sponsor's protocol ID
- R-06-472
- Other IDs
- 122006
- Status last verified
- Nov 2018
- First submitted
- 30 Aug 2007
- Last updated
- 6 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of 12 mg/kg Intravenous Mesna on Plasma Total Homocysteine Concentration in Patients With End-stage Renal Disease Requiring Hemodialysis
- ClinicalTrials.gov ID
- NCT00524199
- Acronym / sponsor ID
- R-06-472
- Conditions
- End Stage Renal Disease
- Keywords
- homocysteine, hemodialysis, mesna
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Mar 2007 (actual)
- Study completion
- Jun 2007 (actual)
- First posted
- 3 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: SalineSaline IV infusion over five minutes at the beginning of dialysis. |
| Mesna | Active comparator | Drug: Mesna12 mg/kg mesna IV infusion over five minutes at the beginning of dialysis. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with end-stage renal disease who have received hemodialysis thrice weekly for at least 90 days
- Serum albumin > 30 g/L.
Key exclusion criteria (2 listed)
- Patients who refuse to sign a letter of informed consent
- Women who are or are trying to become pregnant or are breast-feeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MesnaAlso: Mesnex, Uromitexan12 mg/kg IV infusion over five minutes at the beginning of dialysis thrice weekly. | Drug | Mesna |
| SalineSaline IV infusion over five minutes at the beginning of dialysis thrice weekly. | Other | Placebo |
Primary outcome
Difference in plasma total homocysteine between placebo and mesna treatments
Time frame: Four weeks
1 secondary outcome
Excretion of mesna during hemodialysis
Time frame: duration of dialytic session
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David J Freeman, MSc, PhD principal investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Andrew A House, MD principal investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mesna and Saline in people with End Stage Renal Disease, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in plasma total homocysteine between placebo and mesna treatments (time frame: Four weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2018.