Effect of Vitamin K2 (MK7) on Cardiovascular and Bone Disease in Dialysis Patients: A Prospective, Randomized Placebo-controlled Double Blind Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 123
- 试验地点
- 2
- 主要终点
- For RenaKvit-vessel: Changes in arterial stiffness assessed by pulse wave examination reflecting vascular calcification (unit: m/s).
研究概览
简要总结
Cardiovascular disease (CVD) is the most frequent cause of death in patients (ptt.) with chronic kidney disease (CKD). Compared to the general population death due to CVD is 10-20 times higher in CKD ptt. being treated with hemodialysis. Vascular calcification and hence arterial stiffness is of great importance for the high incidence of CVD.
CKD ptt. in dialysis treatment also have a 3 times higher risk of bone fractures. Both vertebral and other fractures of low energy are associated with a high mortality.
Matrix Gla Protein (MGP) is an important inhibitor of vascular calcification and Osteocalcin (OC) is an important regulator of bone metabolism. The function of both MGP and OC depend on vitamin K.
Vitamin K is supplied with food. The content is low in food recommended to CKD ptt. which is reflected in very low concentrations of vitamin K in their blood samples. A correlation between vitamin K level, incidence of vascular calcification and bone density has been proven; yet there are no trials elucidating the clinical effect of vitamin K on vascular calcification or bone strength.
The investigators will conduct a randomized placebo controlled trial examining the clinical effects of vitamin K2 on vascular calcification and bone mineralization in order to prevent and treat CVD and bone disease in CKD ptt.
Primary study endpoints:
- Changes in arterial stiffness assessed by pulse wave examination
- Changes in bone mineral density (BMD) in distal radius assessed by DXA-scans.
Secondary study endpoints:
Changes in coronary artery and valvular calcification assessed by heart-CT-scans, blood pressure, body composition, total and regional BMD, lateral column/aortic calcification score as well as a panel of correlating blood tests.
详细描述
BACKGROUND
Vascular calcification is a significant problem among patients (ptt.) with chronic kidney disease (CKD) and the prevalence of aortic calcification is twice as high as the general population e.g. Cardiovascular disease (CVD) is the most frequent cause of death in ptt. with CKD. Death due to CVD is 10-20 times higher in CKD ptt. being treated with hemodialysis compared to the background population. Whereas atherosclerosis is a dominating cause of CVD in the general population CKD ptt. tend to develop medial calcification and hence arterial stiffness which is thought to be of great importance in the high incidence of CVD.
CKD ptt. in dialysis treatment also have a 3 times higher risk of bone fractures compared to the general population. Both vertebral and other fractures of low energy are associated with a high mortality in CKD ptt.
The genesis of the arteriosclerosis is still unresolved but seems to be multifactorial. The impaired kidney function itself and the treatment so far both seem to be of importance. The vitamin K-dependent Gla proteins; Matrix Gla Protein (MGP) and Osteocalcin (OC) are described as the most potent inhibitors of vascular calcification and osteoporosis. Until recently CKD ptt. have been treated with vitamin K antagonists which just adds to the focus on vitamin K in this progressive, vascular calcification- and bone demineralization process.
Vitamin K is supplied with food. It consists of several subtypes, e.g. vitamin K1 which is transformed into K2 during digestion. The recommended diet for CKD ptt. is low on vitamin K which is reflected in very low concentrations of vitamin K in blood samples from CKD ptt. in hemodialysis. A supplement of vitamin K1 or K2 will make activation possible for MGP and OC by increasing the concentration of vitamin K2.
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
- •Age ≥ 18 years old
- •Life expectancy > 2 years
- •Written consent following oral information
- •Permanent treatment with dialysis ≥ 3 months with either peritoneal or hemodialysis
排除标准
- •Treatment with vitamin K or vitamin K-antagonist by the beginning of the trial or 1 months within.
- •Chronic GI-malabsorption leading to a slower bowel transit (e.g. Celiac disease, Short bowel syndrome).
- •Ongoing malignancy (ongoing treatment/clinical controlled visits or diagnosed less than 5 years ago), excl. Non-Melanoma-Skin-Cancer (NMSC).
- •Abuse of alcohol or other euphoric drug.
- •Women who are pregnant or breast-feeding and women who are in the childbearing age without contraception.
- •Total/subtotal parathyroidectomy
- •Treatment with recombined PTH.
- •Treatment with bisphosphonates or other anti-osteoporotic drugs (Selective Estrogen Reuptake Modulators (SERM), strontium, renalat, denosumab).
- •Only RenaKvit-kar (vessel):
- •Atrial fibrillation/other arrhythmia of significance
- •Aortic stenosis of significance
- •Agatston score < 100 by heart-CT-scan
- •Bilateral upper arm fistula
- •Amputation above metatarsal level
- •Criteria of withdrawal:
- •Kidney transplantation
- •Starting treatment with vitamin K-antagonists
- •Wish to with draw from the participant
- •Unacceptable side effect to ingestion of vitamin K or placebo
- •Reasonable suspicion of lacking compliance regarding medication
结局指标
主要结局
For RenaKvit-vessel: Changes in arterial stiffness assessed by pulse wave examination reflecting vascular calcification (unit: m/s).
时间窗: 2 years
For RenaKvit-bone: Changes in bone mineral density (BMD) in the distal radial bone (unit T-score).
时间窗: 2 years
次要结局
- For RenaKvit-vessel: Changes in coronary vascular and -valve calcification assessed by CT-scans of the heart (unit: Agatston-Score).(2 years)
- For RenaKvit-vessel: Changes in vascular calcification measured by changes in blood pressure measurements (unit: mmHg).(2 years)
- For RenaKvit-bone: Changes in abdominal aortic calcification measured by lateral X-ray of lumbar column (unit: abdominal aortic calcification score).(2 years)
- For RenaKvit-bone: Changes in body composition, BMD in the lumbar column, hip and whole body (unit: T-score).(2 years)