Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 2
- 主要终点
- Change from baseline in circulating MGP level at 12 weeks
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Calcific uremic arteriolopathy (a.k.a. calciphylaxis)
排除标准
- •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)
研究组 & 干预措施
Placebo
Identical appearing placebo orally three times a week after dialysis for 12 weeks
干预措施: Placebo (Other)
Vitamin K
Vitamin K1 (phytonadione) 10 mg orally three times a week after dialysis for 12 weeks
干预措施: Vitamin K (Dietary Supplement)
结局指标
主要结局
Change from baseline in circulating MGP level at 12 weeks
时间窗: Baseline and 12 weeks
次要结局
- Change from baseline in pain at 12 weeks(Baseline and every month for 3 months)
- Change from baseline in combined area of all lesions at 12 weeks(Baseline and every month for 3 months)
- Change from baseline in largest lesion size at 12 weeks(Baseline and every month for 3 months)
研究者
Sagar U. Nigwekar, MD, MMSc
Assistant Physician
Massachusetts General Hospital