Efficacy and Safety of Oral L-Arginine for Pain Relief in Knee Osteoarthritis: a Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 340
- 试验地点
- 1
- 主要终点
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.
研究概览
简要总结
This study will examine the pain-relief efficacy and safety of L-arginine in knee OA patients.
详细描述
Pain is the dominant symptom of knee osteoarthritis (KOA). The main management goal for people with KOA is to control pain without increasing treatment-related adverse effects (AEs). However, the commonly prescribed systemic analgesics have safety concerns, such as increased risk of cardiovascular and gastrointestinal AEs. Therefore, it is urgent to develop safe and effective treatment options.
L-arginine is one of the most commonly used oral nutritional supplements that has been widely used in patients with peripheral arterial disease, cystic fibrosis, and pregnant women with high risk of pre-eclampsia. The supplement has a high safety profile. Previous case-control and cross-sectional studies have found plasma L-arginine levels were lower in patients with knee OA than controls, suggesting that arginine deficiency may increase the risk of OA. The investigators previously observed an inverse dose-response relationship between levels of serum L-arginine and the risk of incident symptomatic KOA. Additionally, the investigators demonstrated that intra-articular injection of L-arginine solution relieved pain symptoms in a surgical rat model of OA. However, there is a paucity of high-quality clinical evidence on the effect of intake of L-arginine supplement on pain relief among patients with symptomatic KOA.
The investigators propose to conduct a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of oral L-arginine in patients with knee OA.
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
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 40 and 80 years.
- •Knee OA according to the American College of Rheumatology (ACR) clinical criteria.
- •Knee pain lasting 3 months or longer and a score of 7 or greater on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (standardized to range from 0-20).
- •Kellgren-Lawrence (KL) grade 2 or
- •Willing to and able to provide written informed consent.
排除标准
- •Any use of NSAIDs or other analgesics in the past two weeks.
- •History of injections of corticosteroids in the past three months or hyaluronic acid in the past 6 months in the index knee.
- •History of arthroscopy or open surgery in the index knee in the past 12 months.
- •History of a knee replacement in the index knee or planning to receive such a procedure within 3 months.
- •History of a severe injury in the index knee.
- •Pain in the index knee caused by inflammatory, autoimmune, neoplastic diseases or other diseases.
- •Abnormal liver or kidney functions, as defined by alanine transaminase or aspartate aminotransferase >two times the upper limit of normal, or blood urea nitrogen or serum creatinine >two times the upper limit of normal.
- •Severe respiratory diseases.
- •History of coronary artery disease and heart failure.
- •Uncontrolled hypertension or diabetes mellitus.
- •Diagnosis of malignant tumors.
- •Pregnant or contemplating pregnancy or breast-feeding.
结局指标
主要结局
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.
时间窗: Baseline, Week 12
WOMAC is a self-administered, disease-specific questionnaire that assesses the severity of OA symptoms. The reliability and validity of WOMAC have been confirmed in many clinical trials. WOMAC subscales consist of pain (5 items), stiffness (2 items), and physical function (17 items). Each item is rated from 0 to 4, totaling scores of 0-20, 0-8, and 0-68 for pain, stiffness, and function subscales, respectively.
次要结局
- Rescue medicine consumption.(Weeks 2, 4, 8 and 12)
- Change From Baseline in Level of C-reactive protein (CRP).(Baseline, Weeks 4, 8 and 12)
- Change From Baseline in Microbiota diversity and composition.(Baseline, Weeks 4, 8 and 12)
- Incidence of adverse events and serious adverse events.(Weeks 2, 4, 8 and 12)
- Change From Baseline in Ultrasound-assessed knee synovitis.(Baseline, Week 12)
- Change From Baseline in WOMAC pain score.(Baseline, Weeks 2, 4 and 8)
- Change From Baseline in Knee pain on a visual analogue scale (VAS).(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in WOMAC total score.(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in Change From Baseline in WOMAC stiffness score.(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in WOMAC function score.(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in Patient global assessment of osteoarthritis (PGA-OA) score.(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in SF-12 questionnaire score.(Baseline, Weeks 2, 4, 8 and 12)
- Change From Baseline in Timed Up and Go Test (TUG).(Baseline, Weeks 4, 8 and 12)
- Change From Baseline in Chair-stand Test.(Baseline, Weeks 4, 8 and 12)