Reducing Perioperative Oxidative Stress to Prevent Postoperative Chronic Pain Following Total Knee Arthroplasty
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: GlyNAC (combination of glycine and n-acetylcysteine), Placebo.
- Who it may be relevant to
- Registry conditions: Osteoarthritis, Knee, Total Knee Arthroplasty, Chronic Postsurgical Pain. Basic parameters: from 50 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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).
Detailed description
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).
Interventions
- Drug 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. - Drug Placebo
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.
Primary outcome measures
- Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours [Time frame: Baseline to 6 months post TKA (approximately 7 months)]
Secondary outcome measures (10)
- Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours [Time frame: Baseline to 6 weeks and 12 months post TKA (13 months)]
- Numeric Rating Scale of Average Pain in the past 24 hours [Time frame: Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)]
- Numeric Rating Scale of Least Pain in the past 24 hours [Time frame: 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. [Time frame: Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)]
- Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) [Time frame: Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)]
- PROMIS Short Form V1.0 - Pain Interference 8a scale [Time frame: Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)]
- Postsurgical Opioid Use (pill count) [Time frame: Post-TKA discharge to 6 weeks, 6 months and 12 months post-TKA (12 months)]]
- Postsurgical Opioid Use (days of opioid use in the past week) [Time frame: 6 weeks, 6 months and 12 months post-TKA (12 months)]
- F2-Isoprostane/Isofuran (IsoP/IsoF) levels [Time frame: Baseline to 4 week pre-TKA assessment, and 6 weeks, 6 months and 12 months post TKA (13 months)]
- Glutathione levels [Time frame: Baseline to 4 week pre-TKA assessment, and 6 weeks, 6 months and 12 months post TKA (13 months)]
Eligibility criteria
Inclusion criteria
- 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.
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Prevention
Study locations
United States · 1 center
- Vanderbilt University Medical Center — Nashville
Identifiers
NCT: NCT06083480 · 231668 · 1R01AG085287-01