Kidney DiseasesPhase 4CACSK2NCT01101698
Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
A Phase 4 study testing Vitamin K2+10μg cholecalciferol and Vitamin D in people with Kidney Diseases and Coronary Artery Calcification, run by Medical University of Lodz at 1 site in Poland.
Trial summary
Vessel calcification is a recognised cardiovascular morbidity risk factor in patients with chronic kidney disease (CKD). Recent reports indicate a significant role of Matrix Gla-protein (MGP) in decreasing calcification processes. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Kidney Diseases, Coronary Artery Calcification
- What is being tested?
- Vitamin K2+10μg cholecalciferol and Vitamin D
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 sitePoland
- Study dates
- Jun 2009to Jun 2011
- Phase
- Phase 4
- 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 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject with chronic kidney disease (creatinine clearance 15-60 ml/min/1,73m2 by Cockroft-Gault formula)
- Patient has a life without dialysis therapy of more than 9 months
- Subject in 30-70 years of age
- Calcium score >10 (as per Agatston scoring system)
Who cannot join
- Atherosclerosis generalisata (myocardial infarction treated with PTCA - Percutaneous Transluminal Coronary Angioplasty or CABG - Coronary Artery Bypass Graft, symptomatic heart insufficiency, cerebrovascular accident)
- Subject with a history of cardiac abnormalities, including symptomatic or asymptomatic arrhythmias (atrial fibrillation)
- Patient with cardiac pacemaker
- Subject requires long-term use of vitamin K antagonists
Trial locations and contacts
1 site in 1 country.
Poland1 site, 1 recruiting
- Recruiting
Department of Nephrology, Hypertension and Kidney Transplantation
Lodz, 90-153
Michał Nowicki, Prof, 0048426776709, nefro@wp.pl
Ilona Kurnatowska, MD, 0048509293095, ilona.kurnatowska@umed.lodz.pl
About this study
Official title: Influence of Vitamin K2 Administration on Vessel Calcification Markers in Patients With Chronic Kidney Disease
Vessel calcification is a recognised cardiovascular morbidity risk factor in patients with chronic kidney disease (CKD). Recent reports indicate a significant role of Matrix Gla-protein (MGP) in decreasing calcification processes. MGP is excretion protein whose mechanism of action is not yet fully explained and which to be activated requires phosphorylation and carboxylation where cofactor is vitamin K. These observations indicate that shortage of vitamin K is a significant risk factor for the development of vessel calcification. Another calcification risk factor in CKD patients are calcium-phosphate disturbances and insufficiency of vitamin D3 which in physiological concentration stimulates MGP transcription. The aim of this study is estimation of influence of vitamin K2 administration over the period of 9 months on vessel calcification in 3.- 5. stage CKD patients.
It is a prospective, randomised double-blind study carried out in parallel groups. 60 patients with CKD (GFR 15-60 ml/min) with calcium score >10 (Agatston scoring system) will be qualified for the study. On the basis of randomised selection, patients will be divided into two groups: 30 patients will be given 90 μg vitamin K2 + 10 μg and cholecalciferol 30 patients will be given only 10 μg cholecalciferol. After a 9-month treatment the image diagnostic will be carried out in order to estimate the degree of vessel calcification.
Read the detailed description
Vessel calcification is a recognised cardiovascular morbidity risk factor in patients with chronic kidney disease (CKD). Recent reports indicate a significant role of Matrix Gla-protein (MGP) in decreasing calcification processes. MGP is excretion protein whose mechanism of action is not yet fully explained and which to be activated requires phosphorylation and carboxylation where cofactor is vitamin K. Immunohistochemical tests showed a high level of un-carboxylated MGP in calcified vessels. These observations indicate that shortage of vitamin K is a significant risk factor for the development of vessel calcification. On the other hand CKD patients often display shortages of this vitamin. Another calcification risk factor in CKD patients are calcium-phosphate disturbances and insufficiency of vitamin D3 which in physiological concentration stimulates MGP transcription. Cranenburg et al. showed a decrease vessel calcification in dialysis patients treated with vitamin K2. Vitamin K2 exists in two forms K1 and K2, however only the K2 form displays calcification decreasing properties. There are currently no similar studies in patients with chronic kidney disease who do not require renal replacement therapy.
The aim of study. The aim of this study is estimation of influence of vitamin K2 administration over the period of 9 months on vessel calcification in 3.- 5. stage CKD patients.
Materials and methods. It is a prospective, randomised double-blind study carried out in parallel groups. 60 patients with CKD (GFR 15-60 ml/min) whose renal replacement therapy is to commence not earlier than in 9 months are planned to be qualified for the study. After familiarizing the patients with the aims of the study and obtaining their written consent, non-invasive tests will be carried out in order to estimate the presence and degree of vessel calcification: common carotid artery intima media thickness (CCA-IMT) by ultrasound examination, coronary artery calcium score (CACS) by multiscan CT as well as the presence of calcified heart valves by ultrasound examination. Patients with calcium score >10 (Agatston scoring system) will be qualified for the study. On the basis of randomised selection, patients will be divided into two groups: 30 patients will be given 90 μg vitamin K2+10 μg cholecalciferol (Vitamin D)and 30 patients will be given only 10 μg cholecalciferol. After a 9-month treatment the image diagnostic will be carried out in order to estimate the degree of vessel calcification. Patients and their basic laboratory test will be evaluated during the study period by a nephrologists on a monthly basis. First, at the commencement of the study, then after 3, 6 and finally after 9 months during the last visit, 10 ml of serum and plasma will be taken and frozen in order to conduct special marking tests: phosphorylated MGP (pMGP), uncarboxylated MGP (ucMGP), 25-OH cholecalciferol, hsCRP.
Scheduling Study Visits:
Visit 0 Screening Period
- Review of inclusion and exclusion criteria
- Obtain informed consent
- Obtain weight and height
- Obtain CACS, CCA-IMT
- Obtain heart ultrasonography
- Review concomitant therapy
Visit 1 - Randomization
- Review of inclusion and exclusion criteria
- Medical history for concomitant disorders (hypertension, heart ischemic diseases, diabetes mellitus)
- Collect blood for serum chemistry (creatinine, albumin, intact PTH, calcium, phosphor, uric acid, lipids, glucose, kaolin-kephalin time, prothrombin index and blood morphology.
- Collect blood for pMGP, ucMGP, 25-OH cholecalciferol, hsCRP
- Review concomitant therapy
- Randomization to: 90 μg vitamin K2+10μg cholecalciferol or 10μg cholecalciferol (Vitamin D) during 9 months
Visit 2,4,5,7,8 Visits every month
- Complete physical examination
- GFR obtain
- Drug dispension
Visit 3,6 and after 9 months:
- Complete physical examination
- GFR obtain
- Collect blood for serum chemistry (creatinine, albumin, intact PTH, calcium, phosphor, uric acid, lipids, glucose, kaolin-kephalin time, prothrombin index and blood morphology.
- Collect blood for pMGP, ucMGP, 25-OH cholecalciferol, hsCRP
- Obtain CACS, CCA-IMT
- Obtain heart ultrasonography
- Review concomitant therapy
- Conditions
- Kidney Diseases, Coronary Artery Calcification
- Being tested
- Vitamin K2+10μg cholecalciferol, Vitamin D
- Keywords
- Vitamin K, chronic kidney disease, coronary artery calcification, intima media thickness
- Medical subject headings
- Kidney Diseases, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin K2+10μg cholecalciferolDrug
Pills of: 90 μg vitamin K2+10μg cholecalciferol once daily during 9 months
Vitamin DDrug
Pills of: 10μg cholecalciferol (Vitamin D)once daily during 9 months
| Study group | Role | What they receive |
|---|---|---|
| Vitamin K2, calcification score changes, vitamin D | Active comparator | 90 μg vitamin K2+10μg cholecalciferol Receives: Drug: Vitamin K2+10μg cholecalciferol; Drug: Vitamin D |
| Vitamin D, calcium score changes | Active comparator | 10μg cholecalciferol (vitamin D) Receives: Drug: Vitamin K2+10μg cholecalciferol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in coronary artery calcification score
Measured: 9 months
Secondary outcomes (1)
Changes in common carotid artery intima media thickness
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2010 (estimated)
- Study startJun 2009
- Primary completionDec 2010 (estimated)
- Study completionJun 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Kidney DiseasesStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Lodz
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01101698
- Sponsor's protocol ID
- CACSK2
- Acronym
- CACSK2
- Status last verified
- Apr 2010
- First submitted
- 9 Apr 2010
- Last updated
- 13 Apr 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pilkey RM, Morton AR, Boffa MB, Noordhof C, Day AG, Su Y, Miller LM, Koschinsky ML, Booth SL. Subclinical vitamin K deficiency in hemodialysis patients. Am J Kidney Dis. 2007 Mar;49(3):432-9. doi: 10.1053/j.ajkd.2006.11.041.
PubMed 17336705Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008 Oct;100(4):593-603.
PubMed 18841280Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG, Kwaijtaal M, Brandenburg VM, Ketteler M, Schurgers LJ. The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res. 2008;45(5):427-36. doi: 10.1159/000124863. Epub 2008 Apr 10.
PubMed 18401181Kurnatowska I, Grzelak P, Masajtis-Zagajewska A, Kaczmarska M, Stefanczyk L, Vermeer C, Maresz K, Nowicki M. Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5. Pol Arch Med Wewn. 2015;125(9):631-40. doi: 10.20452/pamw.3041. Epub 2015 Jul 15.
PubMed 26176325
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Vitamin K2 Administration on Vessel Calcification Markers in Patients With Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT01101698
- Acronym / sponsor ID
- CACSK2 / CACSK2
- Conditions
- Kidney Diseases, Coronary Artery Calcification
- Keywords
- Vitamin K, chronic kidney disease, coronary artery calcification, intima media thickness
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Medical University of LodzUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Dec 2010 (estimated)
- Study completion
- Jun 2011 (estimated)
- First posted
- 12 Apr 2010 (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.
Vessel calcification is a recognised cardiovascular morbidity risk factor in patients with chronic kidney disease (CKD). Recent reports indicate a significant role of Matrix Gla-protein (MGP) in decreasing calcification processes. MGP is excretion protein whose mechanism of action is not yet fully explained and which to be activated requires phosphorylation and carboxylation where cofactor is vitamin K. These observations indicate that shortage of vitamin K is a significant risk factor for the development of vessel calcification. Another calcification risk factor in CKD patients are calcium-phosphate disturbances and insufficiency of vitamin D3 which in physiological concentration stimulates MGP transcription. The aim of this study is estimation of influence of vitamin K2 administration over the period of 9 months on vessel calcification in 3.- 5. stage CKD patients.
It is a prospective, randomised double-blind study carried out in parallel groups. 60 patients with CKD (GFR 15-60 ml/min) with calcium score >10 (Agatston scoring system) will be qualified for the study. On the basis of randomised selection, patients will be divided into two groups: 30 patients will be given 90 μg vitamin K2 + 10 μg and cholecalciferol 30 patients will be given only 10 μg cholecalciferol. After a 9-month treatment the image diagnostic will be carried out in order to estimate the degree of vessel calcification.
Detailed description
Vessel calcification is a recognised cardiovascular morbidity risk factor in patients with chronic kidney disease (CKD). Recent reports indicate a significant role of Matrix Gla-protein (MGP) in decreasing calcification processes. MGP is excretion protein whose mechanism of action is not yet fully explained and which to be activated requires phosphorylation and carboxylation where cofactor is vitamin K. Immunohistochemical tests showed a high level of un-carboxylated MGP in calcified vessels. These observations indicate that shortage of vitamin K is a significant risk factor for the development of vessel calcification. On the other hand CKD patients often display shortages of this vitamin. Another calcification risk factor in CKD patients are calcium-phosphate disturbances and insufficiency of vitamin D3 which in physiological concentration stimulates MGP transcription. Cranenburg et al. showed a decrease vessel calcification in dialysis patients treated with vitamin K2. Vitamin K2 exists in two forms K1 and K2, however only the K2 form displays calcification decreasing properties. There are currently no similar studies in patients with chronic kidney disease who do not require renal replacement therapy.
The aim of study. The aim of this study is estimation of influence of vitamin K2 administration over the period of 9 months on vessel calcification in 3.- 5. stage CKD patients.
Materials and methods. It is a prospective, randomised double-blind study carried out in parallel groups. 60 patients with CKD (GFR 15-60 ml/min) whose renal replacement therapy is to commence not earlier than in 9 months are planned to be qualified for the study. After familiarizing the patients with the aims of the study and obtaining their written consent, non-invasive tests will be carried out in order to estimate the presence and degree of vessel calcification: common carotid artery intima media thickness (CCA-IMT) by ultrasound examination, coronary artery calcium score (CACS) by multiscan CT as well as the presence of calcified heart valves by ultrasound examination. Patients with calcium score >10 (Agatston scoring system) will be qualified for the study. On the basis of randomised selection, patients will be divided into two groups: 30 patients will be given 90 μg vitamin K2+10 μg cholecalciferol (Vitamin D)and 30 patients will be given only 10 μg cholecalciferol. After a 9-month treatment the image diagnostic will be carried out in order to estimate the degree of vessel calcification. Patients and their basic laboratory test will be evaluated during the study period by a nephrologists on a monthly basis. First, at the commencement of the study, then after 3, 6 and finally after 9 months during the last visit, 10 ml of serum and plasma will be taken and frozen in order to conduct special marking tests: phosphorylated MGP (pMGP), uncarboxylated MGP (ucMGP), 25-OH cholecalciferol, hsCRP.
Scheduling Study Visits:
Visit 0 Screening Period
- Review of inclusion and exclusion criteria
- Obtain informed consent
- Obtain weight and height
- Obtain CACS, CCA-IMT
- Obtain heart ultrasonography
- Review concomitant therapy
Visit 1 - Randomization
- Review of inclusion and exclusion criteria
- Medical history for concomitant disorders (hypertension, heart ischemic diseases, diabetes mellitus)
- Collect blood for serum chemistry (creatinine, albumin, intact PTH, calcium, phosphor, uric acid, lipids, glucose, kaolin-kephalin time, prothrombin index and blood morphology.
- Collect blood for pMGP, ucMGP, 25-OH cholecalciferol, hsCRP
- Review concomitant therapy
- Randomization to: 90 μg vitamin K2+10μg cholecalciferol or 10μg cholecalciferol (Vitamin D) during 9 months
Visit 2,4,5,7,8 Visits every month
- Complete physical examination
- GFR obtain
- Drug dispension
Visit 3,6 and after 9 months:
- Complete physical examination
- GFR obtain
- Collect blood for serum chemistry (creatinine, albumin, intact PTH, calcium, phosphor, uric acid, lipids, glucose, kaolin-kephalin time, prothrombin index and blood morphology.
- Collect blood for pMGP, ucMGP, 25-OH cholecalciferol, hsCRP
- Obtain CACS, CCA-IMT
- Obtain heart ultrasonography
- Review concomitant therapy
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin K2, calcification score changes, vitamin D | Active comparator | Drug: Vitamin K2+10μg cholecalciferol, Drug: Vitamin D90 μg vitamin K2+10μg cholecalciferol |
| Vitamin D, calcium score changes | Active comparator | Drug: Vitamin K2+10μg cholecalciferol10μg cholecalciferol (vitamin D) |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subject with chronic kidney disease (creatinine clearance 15-60 ml/min/1,73m2 by Cockroft-Gault formula)
- Patient has a life without dialysis therapy of more than 9 months
- Subject in 30-70 years of age
- Calcium score >10 (as per Agatston scoring system)
Key exclusion criteria (4 listed)
- Atherosclerosis generalisata (myocardial infarction treated with PTCA - Percutaneous Transluminal Coronary Angioplasty or CABG - Coronary Artery Bypass Graft, symptomatic heart insufficiency, cerebrovascular accident)
- Subject with a history of cardiac abnormalities, including symptomatic or asymptomatic arrhythmias (atrial fibrillation)
- Patient with cardiac pacemaker
- Subject requires long-term use of vitamin K antagonists
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 |
|---|---|---|
| Vitamin K2+10μg cholecalciferolPills of: 90 μg vitamin K2+10μg cholecalciferol once daily during 9 months | Drug | Vitamin D, calcium score changes, Vitamin K2, calcification score changes, vitamin D |
| Vitamin DPills of: 10μg cholecalciferol (Vitamin D)once daily during 9 months | Drug | Vitamin K2, calcification score changes, vitamin D |
Primary outcome
Changes in coronary artery calcification score
Time frame: 9 months
1 secondary outcome
Changes in common carotid artery intima media thickness
Time frame: 9 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2010.
- Background: PubMed 17336705Pilkey RM, Morton AR, Boffa MB, Noordhof C, Day AG, Su Y, Miller LM, Koschinsky ML, Booth SL. Subclinical vitamin K deficiency in hemodialysis patients. Am J Kidney Dis. 2007 Mar;49(3):432-9. doi: 10.1053/j.ajkd.2006.11.041.
- Background: PubMed 18841280Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008 Oct;100(4):593-603.
- Background: PubMed 18401181Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG, Kwaijtaal M, Brandenburg VM, Ketteler M, Schurgers LJ. The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res. 2008;45(5):427-36. doi: 10.1159/000124863. Epub 2008 Apr 10.
- Derived from this study: PubMed 26176325Kurnatowska I, Grzelak P, Masajtis-Zagajewska A, Kaczmarska M, Stefanczyk L, Vermeer C, Maresz K, Nowicki M. Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5. Pol Arch Med Wewn. 2015;125(9):631-40. doi: 10.20452/pamw.3041. Epub 2015 Jul 15.
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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.
Department of Nephrology, Hypertension and Kidney Transplantation
Lodz, Poland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vitamin K2+10μg cholecalciferol and Vitamin D in people with Kidney Diseases and Coronary Artery Calcification, run by Medical University of Lodz at 1 site in Poland.
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 4 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 13 Apr 2010. 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 Poland. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in coronary artery calcification score (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01101698, which also lists 4 linked publications.
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 13 Apr 2010.