Clinical Trial: Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy
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.
Detailed Summary:
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, increases carboxylated 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.
Sponsor: Massachusetts General Hospital
Current Primary Outcome: Change from baseline in circulating MGP level at 12 weeks [ Time Frame: Baseline and 12 weeks ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- 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
- Change from baseline in lesion size at 12 weeks [ Time Frame: Baseline and every month for 3 months ]Lesion size is measured in centimeters
Original Secondary Outcome: Same as current
Information By: Massachusetts General Hospital
Dates:
Date Received: October 27, 2014
Date Started: March 2015
Date Completion: December 2017
Last Updated: January 25, 2017
Last Verified: January 2017
