An interventional study of Vitamin K and Placebo in Calciphylaxis and Calcific Uremic Arteriolopathy, sponsored by Massachusetts General Hospital. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-09-17.
Sponsored by Massachusetts General Hospital · Not applicable, Interventional, and Treatment
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.
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.
23 studies on the registry are indexed under Calciphylaxis; 10 are open to participants now.
This study's enrollment of 26 is close to the median of 28 across 12 interventional studies indexed under Calciphylaxis.
Browse Calciphylaxis studies →Massachusetts General Hospital is the lead sponsor of 2,586 studies on the registry; 447 are open to participants now.
Of its 222 completed or terminated interventional studies of FDA-regulated products, 168 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
(*Patients with prior history of thrombosis who are treated with non-warfarin anticoagulant agents (e.g. apixaban, enoxaparin, etc) will be considered for inclusion)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Vitamin K1 (phytonadione) 10 mg orally three times a week after dialysis for 12 weeks
Dietary Supplement: Vitamin K
Identical appearing placebo orally three times a week after dialysis for 12 weeks
Other: Placebo
Oral vitamin K
Oral placebo tablet
Change from baseline in circulating MGP level at 12 weeks
Time frame: Baseline and 12 weeks
Change from baseline in largest lesion size at 12 weeks
Lesion size is measured in centimeters2
Time frame: 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
Time frame: 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
Time frame: Baseline and every month for 3 months
Adverse events
Time frame: Baseline and every month for 3 months
The record gives a start of Mar 2015, a primary completion of Aug 2019 and a completion of Aug 2019. It does not say whether these dates are actual or estimated.
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This study is completed, as verified in Sep 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Vitamin K 1
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