Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy (VitK-CUA)

September 15, 2019 updated by: Sagar U. Nigwekar, MD, MMSc, Massachusetts General Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

26

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Calcific uremic arteriolopathy (a.k.a. calciphylaxis)

Exclusion Criteria:

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Vitamin K
Vitamin K1 (phytonadione) 10 mg orally three times a week after dialysis for 12 weeks
Dietary supplement: Vitamin K
Oral vitamin K
Placebo Comparator: Placebo
Identical appearing placebo orally three times a week after dialysis for 12 weeks
Other: Placebo
Oral placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in circulating MGP level at 12 weeks
Time Frame: Baseline and 12 weeks
Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in largest lesion size at 12 weeks
Time Frame: Baseline and every month for 3 months
Lesion size is measured in centimeters2
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
Lesion size is measured in centimeters2
Baseline and every month for 3 months
Change from baseline in pain at 12 weeks
Time Frame: Baseline and every month for 3 months
Pain is measured using Wong-Baker Faces pain rating scale
Baseline and every month for 3 months

Other Outcome Measures

Outcome Measure
Time Frame
Adverse events
Time Frame: Baseline and every month for 3 months
Baseline and every month for 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

American Heart Association
Harvard University
National Kidney Foundation

Investigators

  • Principal Investigator: Sagar Nigwekar, MD, MMSc, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Actual)

August 1, 2019

Study Completion (Actual)

August 1, 2019

Study Registration Dates

First Submitted

October 27, 2014

First Submitted That Met QC Criteria

October 28, 2014

First Posted (Estimate)

October 30, 2014

Study Record Updates

Last Update Posted (Actual)

September 17, 2019

Last Update Submitted That Met QC Criteria

September 15, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014P001961

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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