Reducing Perioperative Oxidative Stress to Prevent Postoperative Chronic Pain Following Total Knee Arthroplasty

Phase 4RecruitingNCT06083480

Vanderbilt University Medical Center148 enrolled

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).

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

148

Interventions

GlyNAC (combination of glycine and n-acetylcysteine)DRUG

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.

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours

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").

Time frame: Baseline to 6 months post TKA (approximately 7 months)

Secondary Outcomes

Numeric Rating Scale (NRS) Rating of Worst Pain in the past 24 hours

Mean within participant changes in NRS intensity ratings of worst pain in past 24 hours of measurement. 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")

Time frame: Baseline to 6 weeks and 12 months post TKA (13 months)

Numeric Rating Scale of Average Pain in the past 24 hours

Mean within participant changes in NRS intensity ratings of average pain in past 24 hours of measurement. 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").