CalciphylaxisVitK-CUANCT02278692
Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy
A study testing Vitamin K in people with Calciphylaxis and Calcific Uremic Arteriolopathy, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Calcific uremic arteriolopathy a.k.a. calciphylaxis is a vascular calcification disorder seen in dialysis patients. Calcific uremic arteriolopathy has 60-80% one-year mortality and significant morbidity associated with non-healing and extremely painful skin lesions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Calciphylaxis, Calcific Uremic Arteriolopathy
- What is being tested?
- Vitamin K
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to Aug 2019
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Calcific uremic arteriolopathy (a.k.a. calciphylaxis)
Who cannot join
- Warfarin discontinuation contra-indicated (e.g. mechanical heart valve)
- Prior allergic reaction to vitamin K
- Prior history of venous thromboembolism*
- Pregnancy and lactation
- (Patients with prior history of thrombosis who are treated with non-warfarin anticoagulant agents (e.g. apixaban, enoxaparin, etc) will be considered for inclusion)
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Calcific uremic arteriolopathy a.k.a. calciphylaxis is a vascular calcification disorder seen in dialysis patients. Calcific uremic arteriolopathy has 60-80% one-year mortality and significant morbidity associated with non-healing and extremely painful skin lesions. At present, there is no effective treatment for calcific uremic arteriolopathy.
Vitamin K is an important vitamin for inhibiting vascular calcification. It is known to increase the circulating levels of carboxylated Matrix Gla Protein, a potent inhibitor of vascular calcification. However, the effects of vitamin K supplementation in patients with calcific uremic arteriolopathy are unknown.
The purpose of this study is to conduct a pilot randomized controlled trial to examine the effects of oral vitamin K supplementation on circulating levels of anti-calcification factor (carboxylated Matrix Gla Protein) and clinical outcomes in patients with calcific uremic arteriolopathy.
Read the detailed description
Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a vascular calcification disorder associated with 60-80% one-year mortality and significant morbidity. CUA predominantly affects end-stage renal disease (ESRD) patients and presents with painful skin lesions. Although rare (prevalence: 4% in dialysis patients), the incidence of CUA is on the rise as shown by us and others. Mural calcification of dermal arterioles is the hallmark histological finding of CUA. However, there are significant gaps in the understanding of the pathophysiology and risk factors for CUA and there are no effective therapies.
In animal models, vitamin K prevents vascular calcification by serving as a co-factor for Matrix Gla Protein (MGP) carboxylation, a process that converts decarboxylated-MGP (dc-MGP) to carboxylated-MGP (c-MGP). By inhibiting pro-calcification Bone Morphogenic Protein (BMP) ligands, c-MGP acts as a potent vascular calcification inhibitor. uc-MGP is inactive with no vascular calcification inhibitory properties. However, the effects of vitamin K administration on CUA remain unknown.
Aim: To conduct a pilot randomized controlled trial (RCT) of oral vitamin K in CUA.
The investigators will examine the following hypotheses:
Hypothesis 1: Vitamin K therapy, when compared to placebo, reduces uncarboxylated Matrix Gla Protein in chronic hemodialysis patients with CUA.
Hypothesis 2: Vitamin K therapy can be safely administered in chronic hemodialysis patients with CUA.
Hypothesis 3: Vitamin K therapy leads to improvement in CUA pain and average lesion size when compared to placebo in chronic hemodialysis patients.
Study population and procedures: Twenty patients will be enrolled in this pilot RCT over the 2-year study period.
Study Procedures: Patients meeting the eligibility criteria will be consented and randomized to receive either vitamin K (phylloquinone) 10 mg orally three times a week for a total of 12 weeks or identical appearing placebo. Follow-up will occur every 4 weeks during which information will be obtained regarding pain severity, number and size of CUA lesion (s), and adverse events. Blood samples will be taken at baseline and at 12-week follow-up.
Sample processing and assays: Blood samples (plasma and serum, total 30 mL) will be taken at baseline and at 12-week follow-up.
- Conditions
- Calciphylaxis, Calcific Uremic Arteriolopathy
- Being tested
- Vitamin K, Placebo
- Keywords
- Vitamin K, Calciphylaxis, Calcific uremic arteriolopathy, Dialysis, End-stage renal disease
- Medical subject headings
- Calciphylaxis, Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin KDietary supplement
Oral vitamin K
PlaceboOther
Oral placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| Vitamin K | Active comparator | Vitamin K1 (phytonadione) 10 mg orally three times a week after dialysis for 12 weeks Receives: Dietary Supplement: Vitamin K |
| Placebo | Placebo comparator | Identical appearing placebo orally three times a week after dialysis for 12 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in circulating MGP level at 12 weeks
Measured: Baseline and 12 weeks
Secondary outcomes (3)
Change from baseline in largest lesion size at 12 weeks
Lesion size is measured in centimeters2
Measured: Baseline and every month for 3 months
Change from baseline in combined area of all lesions at 12 weeks
Lesion size is measured in centimeters2
Measured: Baseline and every month for 3 months
Change from baseline in pain at 12 weeks
Pain is measured using Wong-Baker Faces pain rating scale
Measured: Baseline and every month for 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2014 (estimated)
- Study startMar 2015
- Primary completionAug 2019
- Study completionAug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for CalciphylaxisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Kidney Foundation, United States, American Heart Association, Harvard University
- Responsible party
- Principal investigator, Sagar U. Nigwekar, MD, MMSc, Massachusetts General Hospital
- Investigators
- Sagar Nigwekar, MD, MMSc, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02278692
- Sponsor's protocol ID
- 2014P001961
- Acronym
- VitK-CUA
- Status last verified
- Sep 2019
- First submitted
- 27 Oct 2014
- Last updated
- 17 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nigwekar SU, Brunelli SM, Meade D, Wang W, Hymes J, Lacson E Jr. Sodium thiosulfate therapy for calcific uremic arteriolopathy. Clin J Am Soc Nephrol. 2013 Jul;8(7):1162-70. doi: 10.2215/CJN.09880912. Epub 2013 Mar 21.
PubMed 23520041Nigwekar SU, Bhan I, Turchin A, Skentzos SC, Hajhosseiny R, Steele D, Nazarian RM, Wenger J, Parikh S, Karumanchi A, Thadhani R. Statin use and calcific uremic arteriolopathy: a matched case-control study. Am J Nephrol. 2013;37(4):325-32. doi: 10.1159/000348806. Epub 2013 Mar 21.
PubMed 23548843Nigwekar SU, Bloch DB, Nazarian RM, Vermeer C, Booth SL, Xu D, Thadhani RI, Malhotra R. Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis. J Am Soc Nephrol. 2017 Jun;28(6):1717-1722. doi: 10.1681/ASN.2016060651. Epub 2017 Jan 3.
PubMed 28049648Nigwekar SU, Zhao S, Wenger J, Hymes JL, Maddux FW, Thadhani RI, Chan KE. A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors. J Am Soc Nephrol. 2016 Nov;27(11):3421-3429. doi: 10.1681/ASN.2015091065. Epub 2016 Apr 14.
PubMed 27080977Cozzolino M, Mangano M, Galassi A, Ciceri P, Messa P, Nigwekar S. Vitamin K in Chronic Kidney Disease. Nutrients. 2019 Jan 14;11(1):168. doi: 10.3390/nu11010168.
PubMed 30646590D Shirsat P, Sonavane K, Botana LR, Sachdeva B. Calciphylaxis in the Upper GI Tract in an ESRD Patient: An Atypical Presentation and Review of Literature. Case Rep Nephrol. 2025 Dec 11;2025:3967671. doi: 10.1155/crin/3967671. eCollection 2025.
PubMed 41472909Krishnasamy R, Jardine MJ; BEAT-Calci Trialists. Adaptive Designs for Clinical Trials in Nephrology. J Am Soc Nephrol. 2025 Jan 1;36(1):147-149. doi: 10.1681/ASN.0000000000000497. Epub 2024 Aug 26. No abstract available.
PubMed 39186385
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy
- ClinicalTrials.gov ID
- NCT02278692
- Acronym / sponsor ID
- VitK-CUA / 2014P001961
- Conditions
- Calciphylaxis, Calcific Uremic Arteriolopathy
- Keywords
- Vitamin K, Calciphylaxis, Calcific uremic arteriolopathy, Dialysis, End-stage renal disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Kidney Foundation, United States, American Heart Association, Harvard University
- Study start
- Mar 2015
- Primary completion
- Aug 2019 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 30 Oct 2014 (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.
Calcific uremic arteriolopathy a.k.a. calciphylaxis is a vascular calcification disorder seen in dialysis patients. Calcific uremic arteriolopathy has 60-80% one-year mortality and significant morbidity associated with non-healing and extremely painful skin lesions. At present, there is no effective treatment for calcific uremic arteriolopathy.
Vitamin K is an important vitamin for inhibiting vascular calcification. It is known to increase the circulating levels of carboxylated Matrix Gla Protein, a potent inhibitor of vascular calcification. However, the effects of vitamin K supplementation in patients with calcific uremic arteriolopathy are unknown.
The purpose of this study is to conduct a pilot randomized controlled trial to examine the effects of oral vitamin K supplementation on circulating levels of anti-calcification factor (carboxylated Matrix Gla Protein) and clinical outcomes in patients with calcific uremic arteriolopathy.
Detailed description
Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a vascular calcification disorder associated with 60-80% one-year mortality and significant morbidity. CUA predominantly affects end-stage renal disease (ESRD) patients and presents with painful skin lesions. Although rare (prevalence: 4% in dialysis patients), the incidence of CUA is on the rise as shown by us and others. Mural calcification of dermal arterioles is the hallmark histological finding of CUA. However, there are significant gaps in the understanding of the pathophysiology and risk factors for CUA and there are no effective therapies.
In animal models, vitamin K prevents vascular calcification by serving as a co-factor for Matrix Gla Protein (MGP) carboxylation, a process that converts decarboxylated-MGP (dc-MGP) to carboxylated-MGP (c-MGP). By inhibiting pro-calcification Bone Morphogenic Protein (BMP) ligands, c-MGP acts as a potent vascular calcification inhibitor. uc-MGP is inactive with no vascular calcification inhibitory properties. However, the effects of vitamin K administration on CUA remain unknown.
Aim: To conduct a pilot randomized controlled trial (RCT) of oral vitamin K in CUA.
The investigators will examine the following hypotheses:
Hypothesis 1: Vitamin K therapy, when compared to placebo, reduces uncarboxylated Matrix Gla Protein in chronic hemodialysis patients with CUA.
Hypothesis 2: Vitamin K therapy can be safely administered in chronic hemodialysis patients with CUA.
Hypothesis 3: Vitamin K therapy leads to improvement in CUA pain and average lesion size when compared to placebo in chronic hemodialysis patients.
Study population and procedures: Twenty patients will be enrolled in this pilot RCT over the 2-year study period.
Study Procedures: Patients meeting the eligibility criteria will be consented and randomized to receive either vitamin K (phylloquinone) 10 mg orally three times a week for a total of 12 weeks or identical appearing placebo. Follow-up will occur every 4 weeks during which information will be obtained regarding pain severity, number and size of CUA lesion (s), and adverse events. Blood samples will be taken at baseline and at 12-week follow-up.
Sample processing and assays: Blood samples (plasma and serum, total 30 mL) will be taken at baseline and at 12-week follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin K | Active comparator | Dietary Supplement: Vitamin KVitamin K1 (phytonadione) 10 mg orally three times a week after dialysis for 12 weeks |
| Placebo | Placebo comparator | Other: PlaceboIdentical appearing placebo orally three times a week after dialysis for 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Calcific uremic arteriolopathy (a.k.a. calciphylaxis)
Key exclusion criteria (5 listed)
- Warfarin discontinuation contra-indicated (e.g. mechanical heart valve)
- Prior allergic reaction to vitamin K
- Prior history of venous thromboembolism*
- Pregnancy and lactation
- (Patients with prior history of thrombosis who are treated with non-warfarin anticoagulant agents (e.g. apixaban, enoxaparin, etc) will be considered for inclusion)
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 KOral vitamin K | Dietary supplement | Vitamin K |
| PlaceboOral placebo tablet | Other | Placebo |
Primary outcome
Change from baseline in circulating MGP level at 12 weeks
Time frame: Baseline and 12 weeks
3 secondary outcomes
Change from baseline in largest lesion size at 12 weeks
Time frame: Baseline and every month for 3 months
Change from baseline in combined area of all lesions at 12 weeks
Time frame: Baseline and every month for 3 months
Change from baseline in pain at 12 weeks
Time frame: Baseline and every month for 3 months
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 17 Sep 2019.
- Background: PubMed 23520041Nigwekar SU, Brunelli SM, Meade D, Wang W, Hymes J, Lacson E Jr. Sodium thiosulfate therapy for calcific uremic arteriolopathy. Clin J Am Soc Nephrol. 2013 Jul;8(7):1162-70. doi: 10.2215/CJN.09880912. Epub 2013 Mar 21.
- Background: PubMed 23548843Nigwekar SU, Bhan I, Turchin A, Skentzos SC, Hajhosseiny R, Steele D, Nazarian RM, Wenger J, Parikh S, Karumanchi A, Thadhani R. Statin use and calcific uremic arteriolopathy: a matched case-control study. Am J Nephrol. 2013;37(4):325-32. doi: 10.1159/000348806. Epub 2013 Mar 21.
- Background: PubMed 28049648Nigwekar SU, Bloch DB, Nazarian RM, Vermeer C, Booth SL, Xu D, Thadhani RI, Malhotra R. Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis. J Am Soc Nephrol. 2017 Jun;28(6):1717-1722. doi: 10.1681/ASN.2016060651. Epub 2017 Jan 3.
- Background: PubMed 27080977Nigwekar SU, Zhao S, Wenger J, Hymes JL, Maddux FW, Thadhani RI, Chan KE. A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors. J Am Soc Nephrol. 2016 Nov;27(11):3421-3429. doi: 10.1681/ASN.2015091065. Epub 2016 Apr 14.
- Background: PubMed 30646590Cozzolino M, Mangano M, Galassi A, Ciceri P, Messa P, Nigwekar S. Vitamin K in Chronic Kidney Disease. Nutrients. 2019 Jan 14;11(1):168. doi: 10.3390/nu11010168.
- Derived from this study: PubMed 41472909D Shirsat P, Sonavane K, Botana LR, Sachdeva B. Calciphylaxis in the Upper GI Tract in an ESRD Patient: An Atypical Presentation and Review of Literature. Case Rep Nephrol. 2025 Dec 11;2025:3967671. doi: 10.1155/crin/3967671. eCollection 2025.
- Derived from this study: PubMed 39186385Krishnasamy R, Jardine MJ; BEAT-Calci Trialists. Adaptive Designs for Clinical Trials in Nephrology. J Am Soc Nephrol. 2025 Jan 1;36(1):147-149. doi: 10.1681/ASN.0000000000000497. Epub 2024 Aug 26. No abstract available.
- Related InfoLink 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.
Sagar Nigwekar, MD, MMSc principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin K in people with Calciphylaxis and Calcific Uremic Arteriolopathy, run by Massachusetts General Hospital 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 1 inclusion and 5 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 17 Sep 2019. 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. 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.
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?
Change from baseline in circulating MGP level at 12 weeks (time frame: Baseline and 12 weeks). 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 NCT02278692, which also lists 7 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 17 Sep 2019.