Efficacy and Safety of Melatonin for Pain Relief in Knee Osteoarthritis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 340
- 试验地点
- 1
- 主要终点
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.
研究概览
简要总结
By recruiting knee osteoarthritis patients and treating them with melatonin, this study aims to determine the efficacy and safety of melatonin in alleviating pain in this patient population.
详细描述
Knee osteoarthritis (KOA) is a major source of pain and disability among adults worldwide, but the treatment options for patients with painful KOA are inadequate. The current first-line oral drugs have only small to moderate benefits, and some may have serious adverse effects. Therefore, it is important to identify novel therapeutic medications with satisfactory efficacy and acceptable side-effect profiles for KOA.
Melatonin (N-acetyl-5-methoxytryptamine), an indolamine mainly secreted in the pineal gland, is generated from the amino acid tryptophan via derivatization reactions. There are numerous experimental and clinical data supporting the analgesic role of melatonin. In experimental studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in people with chronic painful conditions, such as fibromyalgia, irritable bowel syndrome, and migraine. In an animal OA study, the investigators found that melatonin reverses pain behaviors and synovial inflammation, and down-regulates pain sensitization-related neuromediators in the synovium. These findings suggest that melatonin may be potentially effective in treating OA-related pain. However, there is a paucity of high-quality clinical evidence from human studies.
The investigators propose to conduct a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of 12 weeks treatment with oral melatonin on pain and function in patients with KOA.
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 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 cardiopulmonary diseases.
- •Uncontrolled hypertension or diabetes mellitus.
- •Diagnosis of malignant tumors.
- •Pregnant or contemplating pregnancy or breastfeeding.
- •Any use of melatonin supplement before enrollment within 30 days.
- •Allergic to melatonin or its preparation.
- •Any use of anti-depressive/psychotropic drugs.
结局指标
主要结局
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
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.(Baseline, Weeks 2, 4, 6, 8 and 10)
- Knee pain on a visual analogue scale (VAS).(Baseline, Weeks 2, 4, 6, 8, 10, and 12)
- SF-12 questionnaire.(Baseline, Weeks 2, 4, 6, 8, 10 and 12)
- Pittsburgh Sleep Quality Index (PSQI).(Baseline, Weeks 2, 4, 6, 8, 10 and 12)
- Timed Up and Go Test (TUG).(Baseline, Weeks 4, 8, and 12)
- 20-m Walk Test.(Baseline, Weeks 4, 8, and 12)
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score.(Baseline, Weeks 2, 4, 6, 8, 10 and 12)
- Ultrasound-assessed knee synovitis.(Baseline, Week 12)
- C-reactive protein (CRP).(Baseline, Weeks 4, 8, and 12)
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) stiffness score.(Baseline, Weeks 2, 4, 6, 8, 10 and 12)
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score.(Baseline, Weeks 2, 4, 6, 8, 10 and 12)
- Hospital Anxiety and Depression Scale (HADS).(Baseline, Weeks 2, 4, 6, 8, 10 and 12)
- Rescue medicine consumption.(Weeks 2, 4, 6, 8, 10 and 12)
- Incidence of adverse events and serious adverse events.(Weeks 2, 4, 6, 8, 10 and 12)
- Patient global assessment of osteoarthritis (PGA-OA).(Baseline, Weeks 2, 4, 6, 8, 10 and 12)
- Chair-stand Test.(Baseline, Weeks 4, 8, and 12)
- Microbiota diversity and composition.(Baseline, Weeks 4, 8, and 12)