Complication of HemodialysisNCT00568399
Sodium Thiosulfate Treatment of Vascular Calcification in ESRD
A study testing sodium thiosulfate in people with Complication of Hemodialysis and Cardiovascular Diseases, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Cardiovascular disease is the major cause of death in the hemodialysis population and calcification of the major arteries (coronary, aorta, and carotid) are a play a central role in this process. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Complication of Hemodialysis, Cardiovascular Diseases
- What is being tested?
- sodium thiosulfate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2007to Nov 2009
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hemodialysis patient with thrice weekly treatments
- Coronary artery calcium score greater than 50
- Age greater than 18
- Compliant with hemodialysis treatments
- Informed consent
Who cannot join
- Allergy to sodium thiosulfate
- Pregnancy
- Incarceration
- Enrollment in another study
- Life expectancy less than 5 months
- Expectation of recovery of renal function
- Urine output of greater than 200 ml/day or contrast allergy will not receive intravenous contrast
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Sodium Thiosulfate Treatment on Vascular Calcification in End Stage Renal Failure Patients
Cardiovascular disease is the major cause of death in the hemodialysis population and calcification of the major arteries (coronary, aorta, and carotid) are a play a central role in this process. The major causes of the calcification are many, including high levels of phosphorus, low levels of inhibitors of calcification, positive calcium balance, and oxidative stress. Once vascular calcification is present, it is usually progressive. There is no known treatment to reverse established vascular calcification.
Sodium thiosulfate has been used extensively and safely to treat calcific uremic arteriopathy (a disease, in part due to calcification of small arteries) in dialysis patients. It increases the solubility of calcium by up to 100,000 fold and is also a potent anti-oxidant. It therefore has to potential to also decrease the amount of calcium in large arteries in dialysis patients and, hence improve survival.
We will study hemodialysis (HD) patients at high risk for cardiovascular disease and death by obtaining a multidetector computerized tomography (MDCT) Scan of the coronary arteries, carotid arteries and aorta and an assessment of coronary artery stenoses by a simultaneous intravenous infusion of contrast. At the same setting, we will perform tests of pulse wave velocity (PWV) and carotid ultrasound carotid intima-media thickness(CIMT)studies. In those patients at high risk for cardiovascular death, defined as a coronary artery calcification score (CACS)of greater than 50, sodium thiosulfate at a dose of 12.5-25 gm/1.73 M2 will be infused over 15-30 minutes after each dialysis treatment for 5 months. The above studies will then be repeated.
Read the detailed description
Hypothesis 1: The treatment of HD patients with high CAC scores with sodium thiosulfate for 5 months will decrease the amount of calcium in their coronary arteries.
Patients who are at high risk for having coronary calcification (history of MI, ischemic heart disease, peripheral or carotid artery disease) will be selected to undergo testing. We will recruit 60 HD patients receiving treatment in our units to undergo MDCT scanning along with non-invasive testing of PWV and CIMT. Assuming that 60% will have a CAC score of ≥50, 36 patients will be treated with sodium thiosulfate. We will administer 25% sodium thiosulfate solution (American Reagent Laboratories, Shirley, NY) at a dose of 12.5-25g/1.73m2 per over 15-30 minutes after each hemodialysis session for a total of 60 treatments (5 months). Assuming a 35% attrition rate, 23 patients will complete the entire protocol and undergo a repeat study of the initial battery of tests.
Rationale for treatment with sodium thiosulfate: Sodium thiosulfate, used as an antidote for cyanide poisoning for more than a century, is also an anti-oxidant, and binds with calcium to form a highly soluble calcium thiosulfate salt. The solubility of calcium thiosulfate salt is 250-100,000 fold higher than calcium oxalate or calcium phosphate salt. It has been used to treat recurrent calcium kidney stones and tumoral calcinosis (ectopic calcification usually around joints). It has also been used successfully in treating calcific uremic arteriopathy, a disease of small artery and soft tissue calcification, in several studies of dialysis patients and in our own experience of 5 patients. By 2 months there is radiological evidence of reduction in soft tissue calcification. Unpublished data also have demonstrated regression of established aortic calcification in uremic rats.
Sodium thiosulfate is a FDA approved medication for the treatment of cyanide poisoning. It is classified by the FDA as "generally recognized as safe". There are no known contraindications. The only side effects reported during intravenous (IV) administration in ESRD patients are nausea, vomiting and hyperosmia during the administration, which can be alleviated by pre-administration of anti-emetic medications. Sodium thiosulfate is slowly given through the dialysis venous line toward the end of HD treatments. The selected dose for this pilot study is the same as that used for the treatment of calcific uremic arteriopathy.
We will freeze 10 ml of serum obtained prior to and then monthly during treatment for subsequent analyses. Included in the analysis will be Fetuin-A levels but other relevant markers will be considered. Blood will also be frozen for future genomic studies.
- Being tested
- sodium thiosulfate
- Keywords
- Coronary, Calcification, Dialysis, Thiosulfate, Cardiovascular
- Medical subject headings
- Cardiovascular Diseases, Calcinosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium thiosulfateDrug
sodium thiosulfate 12.5-25 gm/M2 after each thrice weekly hemodialysis treatments for 5 months.
| Study group | Role | What they receive |
|---|---|---|
| Active Treatment | Experimental | This is the only arm and involves active treatment with sodium thiosulfate in those subjects with high coronary artery calcium scores. Receives: Drug: sodium thiosulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Annualized Coronary Calcium Volume Score After Treatment With Sodium Thiosulfate.
We will compare the annualized coronary calcium volume score obtained at the baseline CT of the coronary arteries with another CT obtained of the same coronary arteries following 5 months of sodium thiosulfate treatment.
Measured: 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2007 (estimated)
- Study startDec 2007
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Complication of HemodialysisStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Barnes-Jewish Hospital, Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- James A Delmez, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00568399
- Sponsor's protocol ID
- HRPO 07-0331
- Status last verified
- Nov 2012
- First submitted
- 5 Dec 2007
- Last updated
- 20 Nov 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Sodium Thiosulfate Treatment on Vascular Calcification in End Stage Renal Failure Patients
- ClinicalTrials.gov ID
- NCT00568399
- Acronym / sponsor ID
- HRPO 07-0331
- Keywords
- Coronary, Calcification, Dialysis, Thiosulfate, Cardiovascular
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Barnes-Jewish Hospital, Genzyme, a Sanofi Company
- Study start
- Dec 2007
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 6 Dec 2007 (estimated)
- Results
- Posted 6 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cardiovascular disease is the major cause of death in the hemodialysis population and calcification of the major arteries (coronary, aorta, and carotid) are a play a central role in this process. The major causes of the calcification are many, including high levels of phosphorus, low levels of inhibitors of calcification, positive calcium balance, and oxidative stress. Once vascular calcification is present, it is usually progressive. There is no known treatment to reverse established vascular calcification.
Sodium thiosulfate has been used extensively and safely to treat calcific uremic arteriopathy (a disease, in part due to calcification of small arteries) in dialysis patients. It increases the solubility of calcium by up to 100,000 fold and is also a potent anti-oxidant. It therefore has to potential to also decrease the amount of calcium in large arteries in dialysis patients and, hence improve survival.
We will study hemodialysis (HD) patients at high risk for cardiovascular disease and death by obtaining a multidetector computerized tomography (MDCT) Scan of the coronary arteries, carotid arteries and aorta and an assessment of coronary artery stenoses by a simultaneous intravenous infusion of contrast. At the same setting, we will perform tests of pulse wave velocity (PWV) and carotid ultrasound carotid intima-media thickness(CIMT)studies. In those patients at high risk for cardiovascular death, defined as a coronary artery calcification score (CACS)of greater than 50, sodium thiosulfate at a dose of 12.5-25 gm/1.73 M2 will be infused over 15-30 minutes after each dialysis treatment for 5 months. The above studies will then be repeated.
Detailed description
Hypothesis 1: The treatment of HD patients with high CAC scores with sodium thiosulfate for 5 months will decrease the amount of calcium in their coronary arteries.
Patients who are at high risk for having coronary calcification (history of MI, ischemic heart disease, peripheral or carotid artery disease) will be selected to undergo testing. We will recruit 60 HD patients receiving treatment in our units to undergo MDCT scanning along with non-invasive testing of PWV and CIMT. Assuming that 60% will have a CAC score of ≥50, 36 patients will be treated with sodium thiosulfate. We will administer 25% sodium thiosulfate solution (American Reagent Laboratories, Shirley, NY) at a dose of 12.5-25g/1.73m2 per over 15-30 minutes after each hemodialysis session for a total of 60 treatments (5 months). Assuming a 35% attrition rate, 23 patients will complete the entire protocol and undergo a repeat study of the initial battery of tests.
Rationale for treatment with sodium thiosulfate: Sodium thiosulfate, used as an antidote for cyanide poisoning for more than a century, is also an anti-oxidant, and binds with calcium to form a highly soluble calcium thiosulfate salt. The solubility of calcium thiosulfate salt is 250-100,000 fold higher than calcium oxalate or calcium phosphate salt. It has been used to treat recurrent calcium kidney stones and tumoral calcinosis (ectopic calcification usually around joints). It has also been used successfully in treating calcific uremic arteriopathy, a disease of small artery and soft tissue calcification, in several studies of dialysis patients and in our own experience of 5 patients. By 2 months there is radiological evidence of reduction in soft tissue calcification. Unpublished data also have demonstrated regression of established aortic calcification in uremic rats.
Sodium thiosulfate is a FDA approved medication for the treatment of cyanide poisoning. It is classified by the FDA as "generally recognized as safe". There are no known contraindications. The only side effects reported during intravenous (IV) administration in ESRD patients are nausea, vomiting and hyperosmia during the administration, which can be alleviated by pre-administration of anti-emetic medications. Sodium thiosulfate is slowly given through the dialysis venous line toward the end of HD treatments. The selected dose for this pilot study is the same as that used for the treatment of calcific uremic arteriopathy.
We will freeze 10 ml of serum obtained prior to and then monthly during treatment for subsequent analyses. Included in the analysis will be Fetuin-A levels but other relevant markers will be considered. Blood will also be frozen for future genomic studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active Treatment | Experimental | Drug: sodium thiosulfateThis is the only arm and involves active treatment with sodium thiosulfate in those subjects with high coronary artery calcium scores. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Hemodialysis patient with thrice weekly treatments
- Coronary artery calcium score greater than 50
- Age greater than 18
- Compliant with hemodialysis treatments
- Informed consent
Key exclusion criteria (7 listed)
- Allergy to sodium thiosulfate
- Pregnancy
- Incarceration
- Enrollment in another study
- Life expectancy less than 5 months
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 |
|---|---|---|
| sodium thiosulfatesodium thiosulfate 12.5-25 gm/M2 after each thrice weekly hemodialysis treatments for 5 months. | Drug | Active Treatment |
Primary outcome
Change in Annualized Coronary Calcium Volume Score After Treatment With Sodium Thiosulfate.
Time frame: 5 months
We will compare the annualized coronary calcium volume score obtained at the baseline CT of the coronary arteries with another CT obtained of the same coronary arteries following 5 months of sodium thiosulfate treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Effects of Sodium Thiosulfate on Vascular Calcification in End-Stage Renal Disease: A Pilot Study of Feasibility, Safety and Efficacy: Am J Nephrol 2011;33:131-138Link provided by the sponsor.
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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.
James A Delmez, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing sodium thiosulfate in people with Complication of Hemodialysis and Cardiovascular Diseases, run by Washington University School of Medicine at 1 site in United States.
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 5 inclusion and 7 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 20 Nov 2012. 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 United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Annualized Coronary Calcium Volume Score After Treatment With Sodium Thiosulfate. (time frame: 5 months). 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 20 Nov 2012.