Effects of Vitamin K on Lower-extremity Function in Adults with Osteoarthritis: a Randomized Controlled Pilot Trial

维生素 K 对成人骨关节炎患者下肢功能的影响：一项随机对照试验

基本信息

批准号：
10516989
负责人：
SARAH Louise BOOTH
金额：
$ 28.36万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-21 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10516989
关键词：
Address Adherence Adult Affect Aging American Anticoagulation Biological Body Composition Candidate Disease Gene Cartilage Characteristics Clinical Clinical Trials Data Degenerative polyarthritis Development Diet Double-Blind Method Elderly Epidemiology Feasibility Studies Gait speed Generations Genetic Genetic Transcription Genetic Variation Genotype Goals Health Individual International Intervention Intervention Studies Joints Knee Knee Osteoarthritis Lesion Link Lower Extremity Maintenance Measurement Measures Medical Meniscus structure of joint Mission Mus National Institute of Arthritis and Musculoskeletal and Skin Diseases Nuclear Receptors Nutrient Outcome Outcome Study Participant Performance Phase Physical Function Physical Performance Physiological Pilot Projects Placebos Plasma Population Intervention Pre-Clinical Model Prevention Procedures Property Proteins Proteoglycan Public Health Questionnaires Randomized Recommendation Replacement Arthroplasty Research Research Support Risk Role SXR receptor Site Societies Standardization Strategic Planning Supplementation Testing Therapeutic Tissues United States National Institutes of Health Vitamin K Vitamin K 1 Woman aged antagonist articular cartilage base burden of illness clinical research site cohort cost design dietary dietary control disability experience follow-up functional decline genome-wide group intervention high risk in vivo intervention cost matrix Gla protein men novel nutrition pilot trial population based radiological imaging recruit response trial design

项目摘要

PROJECT SUMMARY Knee osteoarthritis (OA) is a leading cause of lower-extremity disability in adults. There is no known cure, so the identification of effective strategies to reduce the consequences of knee OA is important to delay disability and reduce associated cost burden. Multiple lines of biologic, genetic, and epidemiologic evidence support a critical role for vitamin K and vitamin K-dependent proteins (VKDPs) in maintenance of joint health. Vitamin K is an established shortfall nutrient. Preclinical models indicate that vitamin K insufficiency adversely affects articular cartilage. In observational knee OA studies, older adults with low circulating concentrations of vitamin K have poorer lower-extremity function. Vitamin K is required to produce functional VKDPs found in the joint and there is emerging evidence that it regulates transcription of genes in articular cartilage through the nuclear receptor SXR/PXR. Therefore, there are strong physiological underpinnings to support a protective role for vitamin K in knee OA. However, no clinical trials have yet been conducted. To address critical parameters required to design a larger clinical trial, we propose a randomized controlled pilot study in adults with mild to moderate knee OA and low baseline vitamin K status to: (1) Pilot study procedures and assess the feasibility of implementing a larger scale definitive clinical trial of vitamin K supplementation in adults with mild to moderate knee OA and low baseline vitamin K status at two clinical sites; and (2) Determine the responsiveness of performance-based tests of physical function in adults with low vitamin K status and mild to moderate knee osteoarthritis. This randomized pilot study will generate critical data to guide the design of a larger clinical trial to evaluate vitamin K as a potential therapy to mitigate the decline in lower-extremity function among adults with symptomatic knee OA and low vitamin K status. Identifying a single well-tolerated intervention that favorably reduces knee OA progression would represent an important therapeutic breakthrough.

项目概要膝骨关节炎（OA）是成人下肢残疾的主要原因。没有已知的治疗方法，所以确定减少膝关节骨关节炎后果的有效策略对于延缓残疾非常重要并减少相关的成本负担。多种生物学、遗传学和流行病学证据支持维生素 K 和维生素 K 依赖性蛋白 (VKDP) 在维持关节健康中发挥着重要作用。维生素K 是一种已确定的短缺营养素。临床前模型表明维生素 K 不足会对关节软骨。在观察性膝关节 OA 研究中，维生素循环浓度较低的老年人 K的下肢功能较差。维生素 K 是产生关节中功能性 VKDP 所必需的并且有新的证据表明它通过核调节关节软骨中的基因转录受体SXR/PXR。因此，有强大的生理基础来支持保护作用膝盖骨关节炎中的维生素 K。然而，尚未进行任何临床试验。解决关键参数由于需要设计更大规模的临床试验，我们提出了一项针对轻度至轻度成人患者的随机对照试点研究中度膝关节 OA 和低基线维生素 K 状态：(1) 试点研究程序并评估可行性对轻度至中度成人患者补充维生素 K 进行更大规模的明确临床试验两个临床中心的膝关节 OA 和低基线维生素 K 状态； (2) 确定响应性对维生素 K 水平低且膝关节轻度至中度的成年人进行基于表现的身体功能测试骨关节炎。这项随机试点研究将生成关键数据来指导更大规模临床试验的设计评估维生素 K 作为缓解成人下肢功能下降的潜在疗法患有膝关节 OA 症状且维生素 K 水平较低的患者。确定一种耐受性良好的干预措施有利地减少膝关节 OA 的进展将是一个重要的治疗突破。