Reducing Perioperative Oxidative Stress to Prevent Postoperative Chronic Pain Following Total Knee Arthroplasty
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours
研究概览
简要总结
This is a prospective randomized controlled trial that will assess preoperative, perioperative, and long-term oxidative stress (OS); pain; and functional outcomes over a 12 month period and test the hypothesis that a potent antioxidant intervention (glycine + N-acetyl-cysteine(GlyNAC)) reduces oxidative stress and chronic post surgical pain (CPSP) in patients undergoing total knee arthroplasty (TKA).
详细描述
One of the most common surgical procedures performed in older adults is total knee arthroplasty (TKA), with an estimated 1 million TKAs performed annually in the United States. TKA directly addresses the pathology underlying knee joint pain and mobility limitations resulting from osteoarthritis. For most patients, TKA is effective for pain reduction and increasing function. However, a subgroup of 15-20% of TKA patients report unsatisfactory long-term pain outcomes well after postsurgical healing has occurred despite technical success of the procedure. Chronic postsurgical pain (CPSP) following TKA has been reported to be worse than the preoperative pain in 7% of TKA patients at up to 4-years. A potential biological mechanism is perioperative oxidative stress (OS),
The proposed project seeks to confirm the mechanistic role of OS in post-TKA CPSP and test the hypothesis that a perioperative intervention to reduce OS may reduce risk for CPSP post-TKA. This is a prospective randomized controlled trial that will assess preoperative, perioperative, and long-term oxidative stress (OS); pain; and functional outcomes over a 12 month period and test the hypothesis that a potent antioxidant intervention (GlyNAC) reduces OS and CPSP in patients undergoing total knee arthroplasty (TKA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 50 or older
- •Intact cognitive status and ability to provide informed consent (based on cognitive screening with the Mini Mental State Examination)
- •Ability to read and write in English sufficiently to understand and complete study questionnaires
- •Undergoing unilateral primary TKA
- •Medical diagnosis of osteoarthritis
- •Past 24 hour worst numeric rating scale (NRS) pain of at least 4/10.
排除标准
- •Diagnosis of pre-existing neuropathy
- •Untreated hypo/hyperthyroidism
- •Untreated heart disease
- •Alanine transaminase/aspartate transaminase >2x upper-limit of normal range
- •serum creatinine >1.5 mg/dl
- •Pregnancy
- •Complex Regional Pain Syndrome (CRPS) diagnosis prior to undergoing TKA
- •Presence of lower extremity vascular disease, inflammatory or autoimmune disorders, or malignancy
- •Presence of current clinically significant chronic pain conditions outside of the lower extremity ( daily pain for >3 months and greater ≥3/10 in intensity or the focus of medical care)
- •Presence of other medical conditions that in the opinion of the orthopedic surgeon co-investigators would make a patient's study participation unsafe
研究组 & 干预措施
GlyNAC (combination of glycine and n-acetylcysteine)
GlyNAC 200 mg/kg/day (100mg glycine and 100mg N-acetyl-cysteine) will be administered orally in two divided doses each day for four weeks prior to TKA and six weeks postoperatively. The preparation will be a commercially available product of 1:1 ratio of glycine and N-acetyl-cysteine.
干预措施: GlyNAC (combination of glycine and n-acetylcysteine) (Drug)
Placebo (alanine)
Placebo (alanine) 200 mg/kg/day will be administered orally in two divided doses each day for four weeks prior to TKA and six weeks postoperatively.
干预措施: Placebo (Drug)
结局指标
主要结局
Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours
时间窗: Baseline to 6 months post TKA (approximately 7 months)
Mean within participant changes in NRS intensity ratings of worst pain in past 24 hours of measurement at 6 months post TKA. The score is a rating of current acute pain using a 0-100 numeric rating scale (NRS) (0 = "no pain" and 100 = "worst possible pain").
次要结局
- Numeric Rating Scale of Least Pain in the past 24 hours(Baseline to 6 weeks, 6 months and 12 months post TKA (13 months))
- PROMIS Short Form V1.0 - Pain Interference 8a scale(Baseline to 6 weeks, 6 months and 12 months post TKA (13 months))
- Postsurgical Opioid Use (pill count)(Post-TKA discharge to 6 weeks, 6 months and 12 months post-TKA (12 months)])
- Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours(Baseline to 6 weeks and 12 months post TKA (13 months))
- Numeric Rating Scale of Average Pain in the past 24 hours(Baseline to 6 weeks, 6 months and 12 months post TKA (13 months))
- Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of knee pain for average pain over past week of measurement.(Baseline to 6 weeks, 6 months and 12 months post TKA (13 months))
- Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR)(Baseline to 6 weeks, 6 months and 12 months post TKA (13 months))
- Postsurgical Opioid Use (days of opioid use in the past week)(6 weeks, 6 months and 12 months post-TKA (12 months))
- Glutathione levels(Baseline to 4 week pre-TKA assessment, and 6 weeks, 6 months and 12 months post TKA (13 months))
- F2-Isoprostane/Isofuran (IsoP/IsoF) levels(Baseline to 4 week pre-TKA assessment, and 6 weeks, 6 months and 12 months post TKA (13 months))
研究者
Stephen Bruehl, PhD
Professor of Anethesiology
Vanderbilt University Medical Center