Clinical trial NCT06083480: Reducing Perioperative Oxidative Stress to Prevent Postoperative Chronic Pain Following Total Knee Arthroplasty
Official title: Reducing Perioperative Oxidative Stress to Prevent Postoperative Chronic Pain Following Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Osteoarthritis, Knee
Total Knee Arthroplasty
Chronic Postsurgical Pain
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2023-10-16
Enrollment: 148
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, controlled, mixed between/within-subject longitudinal trial
Primary purpose: PREVENTION

Brief summary: 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).

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

Primary outcomes:
measure: Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours
timeFrame: Baseline to 6 months post TKA (approximately 7 months)
Secondary outcomes:
measure: Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours
timeFrame: Baseline to 6 weeks and 12 months post TKA (13 months)
measure: Numeric Rating Scale of Average Pain in the past 24 hours
timeFrame: Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)
measure: Numeric Rating Scale of Least Pain in the past 24 hours
timeFrame: Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)
measure: Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of knee pain for average pain over past week of measurement.
timeFrame: Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)
measure: Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR)
timeFrame: Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)
measure: PROMIS Short Form V1.0 - Pain Interference 8a scale
timeFrame: Baseline to 6 weeks, 6 months and 12 months post TKA (13 months)
measure: Postsurgical Opioid Use (pill count)
timeFrame: Post-TKA discharge to 6 weeks, 6 months and 12 months post-TKA (12 months)]
measure: Postsurgical Opioid Use (days of opioid use in the past week)
timeFrame: 6 weeks, 6 months and 12 months post-TKA (12 months)
measure: F2-Isoprostane/Isofuran (IsoP/IsoF) levels
timeFrame: Baseline to 4 week pre-TKA assessment, and 6 weeks, 6 months and 12 months post TKA (13 months)
measure: Glutathione levels
timeFrame: Baseline to 4 week pre-TKA assessment, and 6 weeks, 6 months and 12 months post TKA (13 months)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Stephen Bruehl, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Frederic T Billings, IV, MD
role: PRINCIPAL_INVESTIGATOR
References: