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

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ClinicalTrials.gov Identifier: NCT02278692
Recruitment Status : Completed
First Posted : October 30, 2014
Last Update Posted : September 17, 2019
Sponsor:
Collaborators:
National Kidney Foundation
American Heart Association
Harvard University
Information provided by (Responsible Party):
Sagar U. Nigwekar, MD, MMSc, Massachusetts General Hospital

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Calciphylaxis Calcific Uremic Arteriolopathy Dietary Supplement: Vitamin K Other: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy
Study Start Date : March 2015
Actual Primary Completion Date : August 2019
Actual Study Completion Date : August 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin K
Drug Information available for: Menadione

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




Primary Outcome Measures :
  1. Change from baseline in circulating MGP level at 12 weeks [ Time Frame: Baseline and 12 weeks ]

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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


Other Outcome Measures:
  1. Adverse events [ Time Frame: Baseline and every month for 3 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02278692


Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Kidney Foundation
American Heart Association
Harvard University
Investigators
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Principal Investigator: Sagar Nigwekar, MD, MMSc Massachusetts General Hospital

Additional Information:
Publications:
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Responsible Party: Sagar U. Nigwekar, MD, MMSc, Assistant Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02278692    
Other Study ID Numbers: 2014P001961
First Posted: October 30, 2014    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019
Keywords provided by Sagar U. Nigwekar, MD, MMSc, Massachusetts General Hospital:
Vitamin K
Calciphylaxis
Calcific uremic arteriolopathy
Dialysis
End-stage renal disease
Additional relevant MeSH terms:
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Calciphylaxis
Calcinosis
Calcium Metabolism Disorders
Metabolic Diseases
Vitamins
Vitamin K
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants